Contents:
Breast carcinoma is the world’s most prevalent type of cancer.The building of predictive cytotoxicity breast cancer models assists permanent synthetic activities and give critical information about structure-activity of novel structure design through a quantitative Structure-Activity Relationship (QSAR) modelling application. Quantitative Structure-Activity Relationships (QSAR) present a model that links pharmacological and biological activities to chemical structures and molecular docking research reveals the medication’s interaction with its targeted enzymes. This review is dedicated for the detailed study of models for designing highly effective breast anticancer MCF7 cells. The Per-ARNT-SIM transcription factor family includes the Aryl hydrocarbon Receptor (AhR), which is a member recognized as a viable novel aim for the cure of breast cancer. The development of a series of 2-phenylacrylonitriles that target AhR has showed enticing and discerning efficacy against malignancy cells while preserving healthy and non-cancerous cell lines. This study aims to use estimating techniques such molecular docking studies, Quantitative Structure-Activity Relationship (QSAR) and QSAR model parameters to more advanced design new effective molecules and analyse the pharmacokinetics “drug-likeliness” assets of the new compounds before they could progress to pre-clinical trial. These investigations also showed that derivatives of 2-(4-fluorophenyl) imidazole-5-one were more potent anti-cancer therapeutic candidates against the MCF-7 cell line. This exemplifies a remarkable medical breakthrough in the fight against breast cancer (MCF-7 cell line).
Background
Rheumatoid Arthritis (RA) is a chronic form of inflammatory disorder where the immune system causes the destruction of bones and cartilage in joints and impacts the quality of life. Few studies have explored the possibility of the involvement of oxidative stress markers in the pathophysiological process of disease progression in RA as well as the beneficial effect of antioxidants. It was discovered that no systematic review had been carried out to support this idea over the previous five years.
Aim
This review is intended to analyse the participation of oxidative stress markers in the origination and development of RA so that they can be a potential biomarker for supportive therapy.
Materials and Methods
This systematic review was carried out as per the PRISMA guidelines. The authors executed a systematic literature search in different search engines for cross-sectional case-control research studies during the period from January 1, 2018 to November 30, 2022. Following inclusion and exclusion criteria, 16 articles have been selected for final analysis.
Results
The evaluated biomarkers in the aforementioned studies countenance the participation of oxidative stress in RA with disease progression. However, additional research will be needed in the future to determine how oxidative stress contributes to the progression of RA and the potential role of antioxidants.
Conclusion
Oxidation biomarkers may be an important tool in the early diagnosis of RA starting at the preclinical stage as well as in determining how the disease is evolving, offering new promise for employing these biomarkers as a focal point for supportive therapy.
Background
To evaluate the value of pharmaceutical care, and sort out the existing problems in the current researches.
Materials and Methods
We established the research strategy and searched seven databases. Two reviewers independently screened the studies, extracted data, conducted the statistical analysis and assessed the quality of full economic evaluations. The pharmaceutical care was divided into 9 types based on the relevant standards of Chinese Hospital Association.
Results
332 studies were included. The methods were mainly cohort studies (n=187, 56.32%), and followed by randomized controlled trials (n=124, 37.35%). Only 23 studies were conducted as full economic evaluations. The Quality of Health Economic Studies score was 61.22±12.80. The most commonly used effect indicators included length of hospital stay (n=166, 50%), prescription rationality rate (n=166, 50%), incidence of adverse reactions (n=117, 35.24%) and course of medication (n=107, 32.23%). For economic indicators, the cost of medication (n=269, 81.02%) and hospitalization (n=113, 34.04%) were the most frequently used indicator. The research results showed that pharmaceutical care could improve the therapeutic effect. 91.45% and 81.42% of the studies revealed that pharmaceutical care could reduce the cost of medication and hospitalization.
Conclusion
Pharmaceutical care can improve the therapeutic effect and save the cost. However, the methodology of pharmaceutical care effect and economic evaluation needs to be further improved.
Aim
This study aimed to qualitatively identify the ranges of the factors involved in the tablet compression process for ivabradine Sustained Release (SR) tablets.
Materials and Methods
A full factorial design of experiments study was used to identify three factors (pre- and main-compression force and paddle rotation time) involved in the compression process of ivabradine SR tablets. For robust tableting, three responses (content uniformity, friability, and dissolution) were evaluated as critical quality attributes via analysis of variance using Design Expert software.
Results
The main compression force significantly influenced dissolution (1 hr, p <0.0001; 3 hr, p <0.0001; and 8 hr, p=0.0002). Precompression and paddle rotation time slightly influenced friability (p=0.0510) and content uniformity (p=0.0968). These results showed that paddle rotation time (0.27-1.37 sec), pre-compression (1.5 kN), and main compression (7.7-9.2 kN) influenced the tablet compression process of the optimal ivabradine SR tablet.
Conclusion
In summary, robust ranges of three factors for tableting were successfully evaluated. It can be concluded that the ranges of tablet compression leading to high quality (low friability and content uniformity, and optimal dissolution) for tableting were successfully observed by the DoE approach.
Objectives
The present study investigated the alternate route of delivery to avoid first pass metabolism and to increase bioavailability by nanosized Liposomes (LP) with Microneedles (MNs) Assistance for the Delivery of Atorvastatin (AVT), a HMG CoA reductase inhibitor in which the role of commercial Epyz derma Roller (poke and patch) MN arrays containing 540 Titanium Microneedles (MNs) with dissimilar micro-needle lengths (0.25, 0.5, 1.5, 2.5 mm) in improving the in vitro permeation of AVT-LP over pig ear skin was evaluated.
Materials and Methods
AVT-LP were formulated and optimized using four methods and evaluated for microscopy, % drug entrapment efficiency, drug-excipient compatibility studies, In vitro drug release studies, In vitro skin permeation studies. Formulation F4 prepared by thin film hydration method with egg lecithin: cholesterol ratio 1:2, found to be having 92.219±0.965 drug entrapment efficiency and 92.53±0.621 drug release within 24 hr with significant physical and chemical stability. The optimized AVT-LP formulation F4 was prepared into a transdermal patch and using Franz diffusion cells, in vitro skin permeation studies were evaluated for a period of 24 hr.
Results and Discussion
The optimized AVT-LP, were <100 nm in diameter and showed an ordered state of good lamellarity. From the dermatokinetic study it was noticeable that the delivery of MN assisted AVT into the excised porcine skin was significantly higher (p <0.05) with cumulative % drug permeation of 90.13±0.231 for 2.5 mm MNs than that from AVT-LP patch without the help of MNs.
Conclusion
Nanosized MN assisted AVT-LP could avoid oral route first pass metabolism and increase bioavailability.
Aim
Glaucoma treatment often involves the topical application of Timolol maleate (TM) to the eye. However, achieving the desired bioavailability via the ocular route can be challenging due to poor retention and penetration of the drug. To address this issue, Gellan Gum (GG) polymer was employed in the current research to formulate nanoparticles of TM to enhance its release during ocular delivery.
Materials and Methods
TM loaded GG Nanoparticles (TMNPs), were formulated by ionotropic gelation method. The study involved the fabrication of different experimental batches of TMNPs, with varying concentrations of gellan gum (0.06% and 0.12%) and aluminium chloride (0.01,0.02, and 0.03%) and evaluating the impact of these concentrations on the particle size and Entrapment Efficiency (EE%), of TMNPs. The optimized batch of prepared TMNPs was further evaluated for different parameters such as DSC, SEM, FTIR, in vitro release, and ex vivo tolerance and permeation studies.
Results
The particle size and EE% of different batches of TMNPs were found to be in the range of 135.2 to 1519 nm and 20.51 to 78.56% respectively. TMNPs showed a prolonged in vitro drug release (62.11%) profile for 12 hr. Ex vivo ocular tolerance studies confirmed the TMNPs to be non-irritant and safe for ocular drug delivery. Permeation studies revealed that a higher amount of TM from TMNPs (1.9 fold) was taken up by goat’s cornea as compared to drug solution.
Conclusion
In conclusion, TMNPs are found to depict sustained release and can be considered potential and safe carriers for the ocular drug delivery of TM.
Introduction
Vinorelbine tartrate is used as a first-line treatment in conjunction with conventional treatments, especially advanced disease including cancer patients.
Objectives
The objective of the study was to develop a polyelectrolyte complex carrier system for Vinorelbine tartarate used for the treatment of Cancer.
Materials and Methods
Polyelectrolyte Complex (PEC) was prepared using entrapment method using gum Kondagogu and chitosan as polymers. Materials and Methods: Vinorelbine tartarate was best complexed with gum Kondagogu and chitosan. Various formulations were developed by changing the gum Kondagogu and chitosan ratios and optimized. The optimized formulations were further characterized for their complex formation, loading efficiency, entrapment efficiency, particle size, FTIR studies, in vitro release, swelling studies.
Results
At Gumkondagogu concentrations exceeding 80%, the highest output of PEC was noted. In comparison to phosphate buffer (pH 6.8), the PEC revealed a reduction in the discharge of vinorelbine tartarate in 0.1 N HCl. Increased medication release and swelling were caused by increasing the Kondagogu gum concentration in PEC. Due to chitosan’s greater degree of swelling in an acidic medium, PEC 1:3 (“Gumkondagogu: chitosan”) having a greater amount of chitosan demonstrated 98% release in just 4.5 hr.
Conclusion
The observation made in the present investigation conclusively proves that the novel hydrogels prepared from gum Kondagogu/chitosan holds a great potential as a natural polymer based delivery device for controlled delivery of drug like Vinorelbine tartarate for the reason to reduce dosing frequency.
Background
The primary goal of the current investigation is to fabricate a transdermal NFs patch-based drug delivery system using Poly-N-Vinyl Caprolactam (PNVCL) blended with sodium alginate to prepared transdermal nanofibrous patch for lymphoma pain and nursing care, with lidocaine and Rosemary oil, as supportive drugs for pain management.
Materials and Methods
The local anaesthetic Lidocaine (LP) and natural drug Rosemary Oil (RO) were loaded into the temperature transition phase of polymer at 35°C. The LP and RO encapsulated gel was grafted onto the electrospun fabricated nanofibrous R-LP@NFs (Lidocaine loaded rosemary oil fabricated nanofibers) patch for thermal responsive delivery. In vitro cumulative release of RO and LP was examined to investigate triggered delivery.
Results
The observed drug release profiles exhibited that higher release at pH 5.5 and 39°C. In order to measure the plasma concentration of lidocaine, patches were administered onto rat model at lymphoma site during the in vivo investigation. The acquired results demonstrated that the thermoresponsive R-LP@NFs patch have the potential to localised delivery system for pain management.
Conclusion
The developed transdermal nanofibrous patch offers a promising approach for the localized delivery of lidocaine and rosemary oil to improve the effective management of lymphoma pain and nursing care. The controlled release of drugs from the patch demonstrates its potential as a targeted drug delivery system, highlighting its suitability for clinical applications in lymphoma pain management.
Background
Rosuvastatin (ROS) is an anti-hyperlipidaemic drug which reduces cholesterol levels, having poor solubility and low bioavailability (<20%). The objective of the present study was to increase ROS bioavailability by formulating nanosponges.
Materials and Methods
Important quality features were identified using the Quality by Design (QbD) method. Central Composite Design (CCD) was utilized to design formulations. Eudragit L-100 (EL-100) and Polyvinyl Alcohol (PVA) were used as polymers and surfactants, respectively. Nanosponges were produced using emulsion solvent evaporation (RF1-RF15). The final formulations were assessed based on parameters including drug-excipient interaction, particle size, surface morphology, Entrapment Efficiency (%EE), and in vitro drug release. The Design Expert-13 (DOE) produced the optimized Formulation (RF16), which was utilized in the in vivo drug release
Results
All Formulations (RF1-RF15) showed particle size of 99±0.84 nm to 305±0.26 nm, %EE 17.8±0.42 to 84.69±0.45, and drug release was 94.33±0.45% to 99.77±0.56% in 4 hr. Optimized Formulation (RF16) showed a particle size of 295±0.35 nm, % EE of 78.54±0.26 %, and drug release study of 95.13±0.63% in 3.5 hr. The in vivo studies showed Cmax Tmax, AUC0-t, AUC0-α, MRT0-α of the pure drug and RF16 of 7.123μg/mL and 14.787 μg/mL, 1.5 and 2.5 hr, 19.56 μg/mL*hr and 25.71 μg/ mL*hr, 23.91 μg/ml*h, and 48.85 μg/mL*hr, 5.04 hr and 3.91 hr, respectively.
Conclusion
The pharmacokinetic parameters RF16 demonstrate a 2-fold enhancement in the bioavailability of ROS nanosponges compared to the pure drug.
Aim
The aim of this study is to investigate the effects of Normal Saline (NS), Activated Charcoal (AC) and Intravenous Lipid Emulsion (ILE) in colchicine poisonings that resulted in death.
Study Design
The research is an experimental study carried out in a medical school animal laboratory.
Materials and Methods
24 female Sprague-Dawley rats were divided into 4 equal groups. After giving Colchicine (1 mg/kg, PO) to all animals, different treatments (NS, AC, ILE) were given to 3 groups. Group 4 was not treated. Colchicine blood samples (0.8 mL) were taken from the vena jugularis externa at 4, 8 and 24 hr and evaluated by liquid chromatography.
Results
While the blood colchicine level decreased in all groups at 24 hr, the highest decrease was observed in the AC group. Compared to the 4th hr, blood colchicine levels at 8 hr decreased by 15.49% in the NS group, 64.55% in the AC group and 34.56% in the ILE group. Blood colchicine levels at 24 hr decreased by 66.1% in the NS group, 73.12% in the AC group, 37.73% in the ILE group and 59.17% in the untreated group compared to the 8th hr.
Conclusion
AC administration is very effective in lowering blood colchicine levels. ILE can be used with NS and AC as an early treatment option for colchicine overdoses. However, further studies are needed for more effective methods in the treatment of colchicine overdose.
Background
Cancer is a multifaceted disease characterized by uncontrolled cell growth and represents a significant global health challenge. The intricate origins of cancer involve various factors that may act independently or collectively, contributing to its initiation and progression and resulting in the dynamic nature of the disease.
Aim
The current focus of research is to elucidate the role of histone acetylation in cancer progression.
Materials and Methods
A key area of interest is histone deacetylation, which intensifies ion-based interactions between negatively charged DNA and positively charged histones. Histone deacetylation, specifically the removal of acetyl groups from histone proteins by Histone Deacetylase 2 (HDAC2), plays a pivotal role in regulating gene expression. The primary objective of this study was to identify molecular inhibitors targeting HDAC2 through Structure-Based Virtual Screening (SBVS) using an extensive MCULE chemical compound database. After the application of stringent filters, 100 promising compounds were selected for further investigation.
Results
Docking simulations using DockThor revealed 16 molecules with superior free binding energies compared to the control (entinostat). Subsequently, ten compounds meeting the Absorption, Distribution, Metabolism and Excretion (ADME) rules were chosen based on the Egan-Egg permeation predictive model. The top two ligands, along with the positive control entinostat, underwent a five-nanosecond molecular dynamics simulation. The evaluation criteria included toxicity profiling, physiochemical properties, lipophilicity, solubility, pharmacokinetics, druglikeness, medicinal chemistry attributes, Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of Gyration (Rg).
Conclusion
Through these analyses, ligand MCULE-5097730104-0-3 emerged as a promising HDAC2 inhibitor, exhibiting potential efficacy in combating cancer progression.
Objectives
Bladder Cancer (BC) is one of the most common malignant tumours of urinary system, with high rates of metastasis and mortality. Methyltransferase-like 14 (METTL14) is an RNA N6-adenosine methyltransferase that can affect the development of tumours by modifying RNA expression. The study aims to uncover the molecular mechanism and biological function of METTLI4 in BC.
Materials and Methods
qRT-PCR assays were employed METTL14 in BC cell lines. MeRIP-qPCR and RIP were used to verify that SRY-related high-mobility-group box 4 (SOX4) modification by m6A is a downstream target of METTL14.
Results
Biological experiments in vitro have demonstrated the biological function of METTL14 on BC cells. In the MGH-U3 cell lines, the expression of METTL14 was significantly down-regulated (p < 0.001), while the expression of SOX4 was significantly up-regulated (p < 0.01). Intervention of METTL14 expression can affect cell proliferation, migration, invasion, apoptosis, as well as the expression of EMT proteins in BC cell lines (p < 0.05). In addition, METTL14 can affect the biological functions of MGH-U3 cells and the expression of EMT proteins through the m6A modification of SOX4.
Conclusion
METTL14 overexpression inhibited the proliferation, migration, invasion, and promoted apoptosis in BC cells, and also downregulated the expression of EMT-related proteins, while these effects were abolished by silencing SOX2. This suggests that METTL14, through its influence on SOX4 m6A modification, plays a crucial role in regulating the biological functions of bladder cancer cells, indicating its potential as a therapeutic target for BC.
Objectives
Hepatitis B cirrhosis is a serious condition caused by the hepatitis B virus, leading to liver fibrosis and vascular proliferation. Current clinical treatments still have limitations, prompting interest in microecological agents and immune-enhancing nutrition. Recent studies indicated the crucial role of intestinal flora imbalance in cirrhosis development, which might be modulated by the “liver-gut” axis. Therefore, this study aimed to investigate the impact of integrating microecological agents and immune-enhanced enteral nutritional support with antiviral therapy on the intestinal flora, mucosal barrier, and immune function in elderly patients with hepatitis B cirrhosis.
Materials and Methods
Eighty cases of elderly patients diagnosed with hepatitis B cirrhosis in our hospital from January 2020 to December 2022 were included in this retrospective study as study subjects. Both groups received oral tenofovir disoproxil fumarate tablets. The control group underwent basic treatments, including hepatoprotection and a specific diet. The observation group received Bifidobacterium bifidum tetragonum in conjunction with immune-enhanced enteral nutritional support. Nutritional status, gut microbiota, cellular immune status, and intestinal mucosal barrier function were compared before and after intervention in both groups.
Results
There were no significant differences in baseline characteristics between the groups. After 30 days of treatment, the observation group exhibited significantly increased Enterococci, Enterobacteriaceae, Bifidobacteria, and Lactobacillus abundance compared to pre-treatment and the control group. Inflammatory response indicators and CD8+ expression in the observation group at 7 days postoperatively were markedly lower than control, while CD4+ and CD4+/CD8+ were significantly higher. Nutritional indicators and intestinal mucosal barrier function were also superior in the experimental group after 30 days.
Conclusion
In conclusion, microecological agents combined with immune-enhancing enteral nutrition support effectively enhance the intestinal mucosal barrier, immune function, and nutritional status in elderly patients with hepatitis B cirrhosis.
Background and Objectives
Selenium is considered one of the essential components of many enzymes, particularly the antioxidant enzymes such as thioredoxin reductase. Vegetables, among other food sources, are common sources of selenium. In the present study, the green synthesis of Selenium nanoparticles (SeNPs) from Ocimum basilicum’ aerial part was carried out, as were the anticancer and hepatoprotective roles of selenium nanoparticles against liver carcinogen acrylamide-induced toxicity.
Materials and Methods
The classification of SeNPs was done by different spectroscopic methods, including UV-spectroscopy, FT-IR, XRD, and HR-TEM. The synthesized SeNPs were tested for their anticancer properties using MTT assays (the normal human liver fibroblast cell line (WISH) and Human liver cancer (HepG2), respectively).
Results
The histopathological studies indicated that the liver acrylamide induced in mice showed necrosis and damage in liver cells, but the treatment of mice with SeNPs, reduced the effect of acrylamide significantly.
Conclusion
The results indicated the protective effect of SeNPs on acrylamide-induced cells both in vitro and in vivo.
Background
The biological activity of thiophene and carbohydrazide derivatives is well known; some of them are included in various anticancer drugs.
Objectives
The main goal of this work was to develop effective, effective and non-toxic compounds with anti-cancer properties. To achieve this goal, we synthesized a new series of N2, N5-bis(1E)- ethylidene thiophene-2,5-dicarbohydrazide derivatives.
Materials and Methods
Thiophene-2,5-dicarbohydrazide reacts with aromatic aldehydes and ethanol to form a new series of derivatives. This work examined the compounds obtained for them in vitro cytotoxic activity against the breast cancer lines MCF-7.
Results
The results of antiproliferative cell inhibition studies showed that some compounds showed high activities compared to standard imatinib drugs.
Conclusion
The most promising compounds D1-D10 were selected to study their inhibitory effects on the MCF-7 cell line, where compound D5 showed the highest activity. All synthesized compounds have no adverse effect on normal cell lines.
Introduction
Urolithiasis is one of the most prevailing diseases in the society. Conventional treatments are symptomatic and are not targeted to direct the dissolution of ureteric calculi. Thus, in this study plants like Cinnamomum verum (Lauraceae) (C. verum) and Nigella sativa (Ranunculaceae) (N. sativa) are selected to assess for their lithotriptic activity.
Materials and Methods
The combinations of hydroalcoholic extract of these plants were prepared (HaNsCv). Ureteric calculi of human origin were sampled from patients post lithotripsy. The sampled calculi were weighed and incubated ex vivo with various concentrations of HaNsCv extract like 50, 100, 200 and 400 mg in tris buffer (pH 7) at 37°C. The change in the size of ureteric calculi was monitored at interval of 24 hr post for a period of 9 days.
Results and Discussion
Amongst various concentration tested, the dissolution of ureteric calculi was initiated within 24 hr at dose 400 mg whereas remaining concentrations exhibited lithotriptic activity after 24 hr of incubation. Dissolution of ureteric calculi observed was found to be both dose dependent and time dependent. At the end on 9th day 100% dissolution of ureteric calculi was observed at dose 400 mg of HaNsCv extract. LCMS study depicted presence of flavonoids like quercetin, rutin, etc., which would have been responsible for the observed lithotriptic effect. Results obtained indicate that HaNsCv possess lithotriptic potential useful for management of urolithiasis.
Background
Plumbago indica L. (PI) is a Thai traditional medicine that has been reported to improve health benefit including anticancer property. Nevertheless, the effects of PI and this mechanism are still less data in lung cancer.
Aim
To investigate and compare the effects of PI root extract with high and low active compound, plumbagin, on the growth inhibition and apoptotic induction in A549 lung cancer cells with underlying mechanism.
Materials and Methods
Antiproliferative effects of PI were examined by Sulforhodamine B (SRB) and colony formation method. Migratory suppression was studied by Wound healing and Matrigel migration assay. Apoptotic induction, ROS formation, and mitochondrial function were explored by flow cytometric method. Western blotting was used to measure the protein expression.
Results
PI extract with high plumbagin level reduced cell viability by dose- and time-dependent than low plumbagin extract and the data was correlated with colony formation assay. Further, the results of migration assay indicated that 50 μg/mL of high plumbagin also caused induction of anti-migratory effects than low plumbagin. For apoptosis, both of PI extract activated the late apoptosis, especially at high dose of PI extract (50 μg/mL) along with stimulation of ROS formation and mitochondrial dysfunction. The mechanism of apoptosis was observed through the induction of expression of active-caspase 3 level correlated with reduction of pro-caspase 3 expression.
Conclusion
Therefore, these anti-cancer activities of the PI extract with high plumbagin could be served as the potential beneficial effects on lung cancer than low plumbagin. Additionally, the study of PI effects in vivo study is now required to support this in vitro study information.
Aim
The study aimed to identify the phytochemical constituents present in the leaves, stems, and roots of H. cordata and perform in silico molecular docking studies of selected common compounds present in all three parts.
Materials and Methods
The phytochemical components were investigated using the headspace solid-phase micro-extraction followed by gas chromatography-mass spectrometry and molecular docking was performed using Autodock Vina v.1.2.0.
Results
β-pinene was found to be the major compound present in stem (73.89%), leaves (66.46%) and roots (42.88%). Four category targets were used for in silico molecular docking of 14 common compounds found in leaves, roots, and stems. The present study showed that the compounds caryophyllene and dihydro-cis-alpha-copaene-8-ol had antibacterial, antioxidant, anti-cancer, and anti-inflammatory activities.
Conclusion
This work demonstrated the great utility of headspace SPME-GC-MS for the investigation of aromatic chemicals in a variety of edible and medicinal spices. With in silico molecular docking, we may look into the potential pharmacological activity of various volatile organic compounds present in H. cordata.
Background
Diabetic Nephropathy (DN) is a common problem in diabetes and is characterized by glomerular dysfunction, hyperfiltration, and ultimately kidney failure.
Objectives
The present study was intended to understand the salutary activities of Saikosaponin D in the Streptozotocin (STZ)-induced DN model.
Materials and Methods
60 mg/kg of STZ was administered to the rats to initiate DN, and they were then treated with Saikosaponin D (10 and 20 mg/kg, respectively) for 10 weeks. Insulin and blood glucose levels were measured using kits. The levels of renal function markers creatinine, urinary protein, Blood Urea Nitrogen (BUN), inflammatory cytokines, Malondialdehyde (MDA), antioxidant enzyme Catalase (CAT), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) activities were analyzed by the corresponding assay kits. A histopathological analysis of kidney tissues was conducted on both control and treated rats.
Results
The Saikosaponin D treatment remarkably reduced blood glucose while boosting body weight and insulin in the DN rats. Creatinine, urinary protein, and BUN levels were considerably reduced by Saikosaponin D. It also diminished pro-inflammatory mediators and MDA levels while boosting antioxidant enzymes. The results of the histopathological analysis also revealed that Saikosaponin D considerably ameliorated STZ-induced histological damage in kidney tissues.
Conclusion
The current findings of this study demonstrate the therapeutic properties of Saikosaponin D in mitigating the development of DN in STZ-induced rats. Therefore, it was clear that Saikosaponin D could be a promising candidate to treat diabetic nephropathy.
Background
A highly malignant tumor, Breast Cancer (BC) has a poor prognosis for patients with the highest mortality rates in women. BC is currently treatable with a limited number of therapeutic strategies.
Aim
Natural compounds with anti-proliferative capabilities are gaining popularity as a way to mitigate the toxicity of radiation and synthetic anti-tumor drugs. Umbelliferone has been reported to possess diverse pharmacological activities, like anti-cancer, anti-inflammation and anti-oxidation properties.
Materials and Methods
In the current investigation, the potential of umbelliferone as an anti-cancer agent for breast cancer was evaluated in MDA-MB-231 cell lines. The influence of umbelliferone on cell viability AO/EtBr, apoptotic induction, MMP levels, ROS generation, cell adhesion assays, apoptotic marker levels and anti-inflammatory has been examined.
Results
The impact of umbelliferone on the cell viability revealed that its cytotoxic potential increased in a dose-dependent pattern and IC50 concentrations were chosen for further experiments. The results showed that apoptosis was induced by umbelliferone in MDA-MB-231 cells by staining with AO/EtBr, triggering ROS pathway and DNA damage level of MMP. The caspase and inflammatory marker levels were also increased upon umbelliferone treatment.
Conclusion
Umbelliferone cytotoxic potential in cells is mediated by inducing apoptosis, which is supported by significant levels of ROS and MMP level as well as the findings of the staining. All these results suggest that umbelliferone can be used as a potent anti-cancer drug for breast cancer cells.
Background
One of the most effective anti-cancer medications used to treat various cancers is Cisplatin (CP). Due to its nephrotoxicity, its usage is restricted. The purpose of this investigation is to assess Marrubiin’s influence in the protection of rats against CP nephrotoxicity.
Materials and Methods
Animals were divided into five groups. The body weight and kidney weight were measured for all the experimental groups. Urine output and blood samples were collected to assess the Blood Urea Nitrogen (BUN) and Creatinine (Cr) present in the experimental animals. Furthermore, the oxidative stress markers, antioxidant enzymes, inflammatory markers and histopathological studies were carried out to assess the impact of Marrubiin treatment in a dose-dependent manner.
Results
We observed that treating animals CP-induced animals with Marrubiin aided in improving kidney function. Marrubiin significantly increased the level of antioxidant enzymes, histopathology conditions and body weight of the animals. It also downregulated the inflammatory markers, levels of BUN and Cr, urine output, kidney weight and oxidative stress markers.
Conclusion
Thus, we conclude that Marrubiin can be used to protect the kidney from injury induced by cisplatin treatment.
Aim
The objective of the current work was to develop and statistically validate a second order derivative method for estimating atenolol in tablet dosage form using UV spectrophotometry.
Materials and Methods
The method validation was done in accordance with ICH recommendations. Atenolol (BSC class III) and hydrochloride (BSC class II) were soluble in 0.1 N NaOH and gave stable absorbance with it, hence 0.1 N NaOH was chosen as a solvent. The wavelengths selected were 226 nm and 274 nm for atenolol and hydrochlorothiazide respectively. The proposed method was validated for parameters like linearity, precision, robustness, accuracy, limit of detection and limit of quantification.
Results
The method was found to be linear with a correlation coefficient (R2) of 0.999 and within a concentration range of 5-60 μg/mL for atenolol and 5-50 μg/mL for hydrochlorothiazide. The analysis of tablet formulation was carried out using second order derivative method and percentage mean assay was found to be 100.4% and 100.9% for atenolol and hydrochlorothiazide respectively. The method was statistically validated showed less % RSD indicating that method is precise, accurate and robust.
Objectives
The present goal of this analytical study is to develop a simple, reliable, sensitive and robust method that can identify Rivaroxaban (RVB) by using high performance thin liquid chromatography. The current study included a degradation study by using different stress conditions in drug and tablets by using HPTLC.
Materials and Methods
The analysis was performed by using the HPTLC CAMAG system compromising Linomat 5 sample applicator at wavelength 284 nm. Mobile phase selected as toluene (3 mL): ethyl acetate (5.5 mL): methanol (1.5 mL): ammonia (0.1 mL) with ten-minute saturation time.
Results
The parameters like linearity and range, LOD and LOQ, accuracy, robustness, precision was studied for validation. RVB was subjected under the circumstance of forced degradation conditions like hydrolysis (base, acid, neutral), thermal, photolysis and oxidation. Using precoated silica plate as a stationary phase, the retention factor for RVB was 0.57±0.05 found. The reported HPTLC method shows a linear graph in the range of 200-1200 ng/band having regression coefficient is 0.9971. The linear regression equation was obtained as y=6.7609x+55.08. The prominent degradation shows at acidic, basic and oxidative conditions. In acidic condition drug was observed more degraded as compare to other conditions.
Conclusion
HPTLC method is useful to identify and separate the degradant using mass spectra. No degradation was observed at thermal and photolytic conditions.
Introduction
Alpha-Ketoanalogues is a dietary supplement drug containing Calcium-DL- 2-hydroxy-4-(methylthio) butyrate (CHMTB) and Calcium-2-oxo-3-phenyl propionate (COPP) for the management of chronic renal disease.
Objectives
In this study, a simple RP-HPLC method has been developed to simultaneously determine Calcium-DL-2-hydroxy-4-(methylthio) butyrate (CHMTB) and Calcium-2-oxo-3-phenyl propionate (COPP) in Alpha-Ketoanalogues Tablets.
Materials and Methods
The compounds were separated in a single run using a Waters XBridge 250 mm x 4.6 mm C18 column with 5μm particle size and 130 Å pore size. Elution was carried out via gradient mode with the UV detector wavelength set at 210 nm. The mobile phase selected was a binary mixture of ammonium hydrogen sulphate buffer (pH 7.0) and acetonitrile at a 1.0 mL/min flow rate.
Results
The retention time of CHMB and COPP was found to be about 7 min and 20 min, respectively. The chromatographic method shows detector linearity in 50-150% of the operating range with the square of correlation coefficient at 0.9998 and 0.9999 for these two compounds, respectively. The parentage recovery of both CHMB and COPP was within 98-102% range. The method validation was carried out per the USP (chapter 1225) and ICH guidelines (Q2-R2). The developed method was found to be specific, precise, linear, robust, and accurate.
Conclusion
This method could be utilized to assay tablet formulation of CHMB and COPP during the in-process and finished product quality control.
Background
Virtual simulation has been widely used in various pharmacy educational institutions worldwide, and it helps students approach the real-world pharmacy practice experience. However, the importance and practice of validating clinical cases among pharmacy educators still need to be improved.
Objectives
To assess the correlation between the success rate of students with reliability statistics, Exploratory Factor Analysis (EFA), and Confirmatory Factor Analysis (CFA).
Materials and Methods
One hundred and fifty students completed the twenty case scenarios comprising patient interviews, medication labeling, and counseling tasks. Students were randomly divided into an exam group (75 students) and a validation group (75 students). In the exam group, student passes percentages and the mean number of successes and failed students were calculated and compared using the students ‘ t-test. Reliability statistics, EFA, and CFA, were performed in the validation group to validate the clinical case scenarios. Spearman’s correlation was used to assess the correlation between the pass percentage of students and Reliability statistics, EFA, and CFA.
Results
The pass percentage of students had a significant positive correlation (p <0.05) with Cronbach’s α, McDonald’s ω percentage of variance, initial Eigen value, Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI). Also, the Root Mean Square Error of Approximation (RMSEA) and Standardized Root Mean Square (SRMR) had a significant negative correlation (p <0.05) with the pass percentage of students. All these findings authenticate the relationship between the reliability, EFA, and CFA, and validated clinical cases significantly impact the pass percentage of students.
Conclusion
Pharmacy educators should ensure the validation of clinical cases, as validated clinical cases can enhance the learning experience. This may help to uplift the pharmacy practice experience and education.
Background
The process for choosing the right talent to further the institution’s objectives is known as faculty selection. In a pharmacy or engineering college, choosing teaching personnel is quite important. The best-qualified candidates for teaching faculty members in pharmacy/ engineering institutions are chosen in this study using an Analytical Hierarchy Process (AHP).
Materials and Methods
AHP analysis is done based on six primary criteria as Ph.D./M. Tech (P/M), Teaching Experience (TE), Industry Experience (IE), Research Publications (RP), Paper Reviewed/ Board Member (PR/BM) and Technical Courses (TC) in the first round and three secondary criteria as an Oral Presentation (OP), Student Feedback (SF) and Interview Performance (IP) in the second round.
Results
First, create a weight matrix and a normalized weight matrix using the first round’s six basic criteria (P/M, TE, IE, RP, PR/BM, and TC) and the second round’s three subsidiary criteria (OP, SF, and IP). The decision makers’ conclusions are consistent, as shown by the Consistency ratio (CR), which is less than 0.10. In both the first round and the second round, applicant 3 gets the highest weighted score when compared to applicant 6. Thus, candidate 3 is chosen as the most suitable teaching faculty member in the final AHP judgment.
Conclusion
In comparison to the initial criteria, the following criteria are more significant when choosing teaching faculty members. Due to the selection of faculty members of colleges and universities in this article, the subsequent round has a larger weighting than the first.
Background
At the study site, Quality team found many incident reports of bleeding due to increased INR in patients on Warfarin anticoagulation therapy. These patients were unaware about adverse effects of anticoagulation therapy and drug-drug/food-drug interactions. Hence to ensure safety in anticoagulation with Warfarin, team of a Pharmacologist, Clinical Pharmacist and Quality manager decided to conduct a clinical audit to improve high alert medication safety with warfarin.
Materials and Methods
After obtaining Institutional Ethics committee approval, clinical audit proposal form was submitted to the Clinical Audit Committee. Clinical Pharmacists took their clinical rounds to identify patients on anticoagulation with warfarin, asked for their consent in local language, reviewed their case files for data and interviewed them. Action plan was made based on the observations in gap analysis conducted from April-May 2018. Interventions were planned to improvise these standards and analysis continued monthly. Bilingual warfarin education leaflets were given to all patients on warfarin therapy.
Results
Improved awareness on drug-drug and food-drug interactions was observed among the patients from 61.50% to 92.30% in one year. Increase in adherence of INR checking from 76.9% to 100% patients. ADRs to warfarin were recognized and action was taken to treat them within 24 hr by the end of one year of the study.
Conclusion
Marked improvement was observed in the patients’ awareness on drug-drug and food-drug interactions as well as INR monitoring, ADR reporting by clinicians and clinical interventions to prevent harm to the patient.
Objectives
An intracranial aneurysm, usually referred to as an abnormal bulge in the wall of an intracranial artery, is the number one cause of subarachnoid hemorrhage and ranks third among cerebrovascular accidents after cerebral thrombosis and hypertensive cerebral hemorrhage. Head CT Angiography (CTA), magnetic resonance Magnetic Resolution Imaging (MRI) and Digital Subtraction Angiography (DSA) are currently common diagnostic methods. Artificial Intelligence (AI) is a new interdisciplinary, which can greatly help doctors diagnose and treat. Many researchers have contributed novel insights to the study of clinical diagnosis of intracranial aneurysms, which serves as the research direction and foundation of this paper. This study aims to explore how to use artificial intelligence technology to assist doctors in the diagnosis of intracranial aneurysms to improve the accuracy and sensitivity of diagnosis.
Materials and Methods
This paper introduced the background of intracranial aneurysm and auxiliary diagnosis system and then carried out academic research and summary on the two key sentences of clinical diagnosis of intracranial aneurysm and the effect of AI auxiliary diagnosis system on clinical diagnosis of intracranial aneurysm. After that, the algorithm model was established and the algorithm was proposed to provide a theoretical basis for the analysis of clinical diagnosis effect of intracranial aneurysms combined with AI auxiliary diagnosis system. Next, the principles and technical methods of the basic theory were analyzed. At the end of the paper, the simulation experiment was carried out and the experiment was summarized and discussed.
Results
A total of 50 patients with intracranial aneurysms were studied in clinical diagnosis. It can be seen that the accuracy and sensitivity of MRI (Magnetic Resolution Imaging) in detecting aneurysms were significantly different from those of CT (Computed Tomography) and DSA (Digital Subtraction Angiography); DSA was significantly superior to CT and MRI in the details and neck of the aneurysm and there was a significant difference between them. At the same time, with the research on the clinical diagnosis effect of intracranial aneurysms, the research on artificial intelligence assisted diagnosis system is also facing new opportunities and challenges.
Conclusion
Intracranial aneurysms should be treated as soon as possible after diagnosis and the judgment rate of DSA for intracranial aneurysms is high.
Background
Melanin is a natural pigment found in various parts of the human body, which gives our skin, hair and eyes their color and protects the skin from ultraviolet light. Hyperpigmentation refers to a common skin condition in which the appearance of darker patches of skin compared to surrounding areas is observed. Tyrosinase inhibitors are able to control the overactivity of tyrosinase. These compounds inhibit the activity of the tyrosinase enzyme and help fade dark spots, melasma and other forms of hyperpigmentation. Pomegranates are found to be effective in treating hyperpigmentation as they are rich in antioxidants, especially polyphenols such as ellagic acid and anthocyanins. These antioxidants help protect skin from free radical damage, such as Ultraviolet (UV) rays, which can cause hyperpigmentation.
Objectives
This study aims at the phytochemical identification of bioactive compounds from Punicagranatum seed extract interacting with tyrosinase.
Materials and Methods
Gas-Chromatography-Mass Spectroscopy (GC-MS), Fourier-transform infrared spectroscopy for phytochemical identification, formulation of cream and in silico tyrosinase inhibition screening for hyperpigmentation were performed.
Results
GC-MS analysis revealed 70 bioactive phytochemicals and based on drug-like properties, ascorbic acid, beta-sitosterol, ellagic acid and gallic acid were docked with tyrosinase. The residues of the substrate and active binding pocket were identified for grid box optimization and docking. In vitro studies were performed on these compounds and proved their inhibitive effects on the tyrosinase enzyme and in curing hyperpigmentation.
Conclusion
Hence, the formulated cream with Punicagranatum seed extract tends to prove its potential application in hyperpigmentation.
Background
Quinoline is a significant heterocyclic moiety involved in several biological activities including inhibition of transient receptor potential vanilloid 1.
Materials and Methods
A series of 5-amino( N-substituted carboxamide)quinoline derivatives (2o-2t) were synthesized through two steps. FT-IR, 1H NMR and mass spectrum techniques were used to confirm these obtained derivatives. Using acetic acid-induced writhing in rats, all the compounds were tested for TRPV1 inhibition by antinociceptive action. The stomach tissue was investigated by histopathology for checking the ability of synthesized derivatives to damage the stomach mucosa. Also, the biochemical analysis of blood serum was carried out to check the nephrotoxicity and hepatotoxicity.
Results
All the derivatives (2o-2t) having the dose of 200 mg/kg gave good TRPV1 inhibition by antinociceptive activity. Among all, the derivatives 2q, 2r and 2s had a percentage inhibition of 43.90%, 34.15% and 39.04% respectively when compared with a dose of 100 mg/kg of Ibuprofen (48.78%).
Conclusion
A novel 5-amino (N -substituted carboxamide) quinoline compounds are shown to be an intriguing place to start for further investigation into potent and reliable TRPV1 inhibitors.
Objectives
The analytical method development and validation for the determination of Favipiravir (FVPR) in pure and tablet dosage forms by LC/MS-MS Technique.
Materials and Methods
A simple LC-MS/MS method was developed for the determination of a new antiviral drug, FVPR in pharmaceutical formulations the separation process was conducted using a Waters X-Bridge Phenyl Hexyl column (150x4.6 mm, 3.5 μm). The elution method employed was isocratic, involving a buffer solution consisting of 1 mL of Formic acid in 1 Litter of water. The mobile phase consisted of a mixture of two components: the aforementioned buffer and Acetonitrile in a 60:40 v/v ratio. The elution was maintained at a flow rate of 1 mL/min, as well as the entire process was carried out at room temperature. The proposed method was validated according to the International Conference on Harmonization (ICH) guidelines. The established method found better outcomes.
Results
The linearity graph was found in the range of 2-40 ngmL-1, and the correlation coefficient value (R2) obtained was found to be 0.9997. The limit of detection and limit of quantification were 4.044 ngmL-1 and 12.253 ngmL-1, respectively. Tremendous recovery outcomes were observed and found to be 99.49%, 100.09.0% and 100.21% for the FVPR at 150% upper, 100% middle and 50% lower concentrations, respectively. For studying Favipiravir, an electrospray ionization source was employed, with ion pairs of mass analysis at m/z 560.28→158.63 for Favipiravir and m/z 607.33→193.48 for the Internal Standard (IS), which was Zanamivir in this case.
Conclusion
All obtained outcomes were complying with the ICH guidelines. The developed method was simple, unique, accurate, robust, precise, and reproducible for the determination of FVPR in tablet formulation. The method is novel and could be adopted in the formulation industry.
Background
Metformin (MET) is a widely prescribed drug for managing Type 2 Diabetes Mellitus (T2DM). Despite the rich clinical experience and advantages, the clinical utility of MET in renal failure patients is limited because of the treatment-related side effects. A novel colon-targeted MET Delayed-Release (DR) dosage form could be a lucrative option for managing T2DM in renal failure patients. MET DR tablets have minimum systemic exposure and are believed to have the same efficacy as other formulations. Physiologically Based Pharmacokinetic (PBPK) modelling can be useful for drug product development, especially for new dosage forms for improving the safety, efficacy, and clinical applicability of off-patented generic drugs.
Objectives
The current study aims to develop a PBPK model for Proto-type (PT) screening of MET DR tablets.
Materials and Methods
MET PBPK model was developed based on the available literature data. Firstly, Intravenous (IV) and oral PBPK models of MET are developed and validated. The developed model was then used to predict the Bioavailability (BA) of PT MET DR tablets using Virtual Bioequivalence (VBE) trials.
Results
The relative bioavailability of the MET DR tablet was about 20% when compared with other MET formulations. The results indicate that the DR formulation could be effective for reducing the BA and systemic exposure of the drug in chronic renal failure patients.
Conclusion
PBPK modelling and VBE trials can successfully demonstrate the Pharmacokinetic (PK) parameters of PK formulations and the lower systemic exposure and site targeting of MET DR tablets could be useful for the management of T2DM in renal failure patients.
Postgraduate education is recognized to improve communication and clinical skills and to have a positive impact on pharmacists’ professional activities and responsibilities. The purpose of this commentary is to present the Swiss postgraduate education model. In Switzerland, since 2018, an authorization to practice independently requires completion of a Federal Specialized Postgraduate Diploma (FSPD). A motivating factor for pharmacists to complete the FSPD is to be authorized to bear more professional responsibilities and to support their career development. The FSPD has contributed to value pharmacists through training to support their role within the healthcare system. These advances have been officially recognized, for example, federal laws were revised in 2019 to allow pharmacists prescribing a certain list of medicines and a scheme was proposed to integrate community pharmacists in the National Vaccination Strategy. Negative impacts related to the training are in relation to its costs that are mostly covered by the trainee pharmacists and/or through a reduction on his/her salary.The increase in the magnitude of participants in postgraduate education since 2018 shows that an external constraint (change in the legislation) acts as a major driver. The Swiss postgraduate model which also includes the linking of clinical practice and accredited trainings through a competency framework whilst meeting the needs of the trainee pharmacists and pharmacies, may serve as example to other countries. However, the impact on participating pharmacists and on the distribution of roles and responsibilities within the community pharmacies’ teams should be evaluated.