Amelioration of endothelial integrity by 3,5,4'-trihydroxy-trans-stilbene against high-fat-diet-induced obesity and -associated vasculopathy and myocardial infarction in rats, targeting TLR4/MyD88/NF-κB/iNOS signaling cascade.

Exacerbated expression of TLR4 protein (foremost pattern recognition receptor) during obesity could trigger NF-κB/iNOS signaling through linker protein (MyD88), predisposed to an indispensable inflammatory response. The induction of this detrimental cascade leads to myocardial and vascular abnormalities. Molecular docking was studied for protein-ligand interaction between these potential targets and resveratrol. The pre-treatment of resveratrol (20 mg/kg/p.o/per day for ten weeks) was given to investigate the therapeutic effect against HFD-induced obesity and associated vascular endothelial dysfunction (VED) and myocardial infarction (MI) in Wistar rats. In addition to accessing the levels of serum biomarkers for VED and MI, oxidative stress, inflammatory cytokines, and histopathology of these tissues were investigated. Lipopolysaccharide (for receptor activation) and protein expression analysis were introduced to explore the mechanistic involvement of TLR4/MyD88/NF-κB/iNOS signaling. Assessment of in-silico analysis showed significant interaction between protein and ligand. The involvement of this proposed signaling (TLR4/MyD88/NF-κB/iNOS) was further endorsed by the impact of lipopolysaccharide and protein expression analysis in obese and treated rats. Moreover, resveratrol pre-treated rats showed significantly lowered cardio and vascular damage measured by the distinct down expression of the TLR4/MyD88/NF-κB/iNOS pathway by resveratrol treatment endorses its ameliorative effect against VED and MI.

Knowledge, attitude and preparedness of healthcare students toward basic life support at King Khalid University, Abha, Kingdom of Saudi Arabia.

BACKGROUND: Worldwide, millions of people die of sudden cardiac arrest every year. A well-timed cardiopulmonary resuscitation (CPR) increases the possibility of survival by two- to fourfolds. This study aimed to assess the knowledge, attitude, and preparedness of health care students toward basic life support (BLS) at King Khalid University. METHODS: A cross-sectional study was conducted among the health care students of King Khalid University from August to October 2020. Data were collected using a pretested, semi-structured questionnaire and the data were analyzed using Statistical Package for the Social Sciences. RESULRS: The total number of participants was 346. Overall, the participant's knowledge regarding the BLS was inadequate. Majority of the participants were not aware of the acronyms used in BLS. The level of education has a significant impact on the knowledge, whereas gender has no significant impact on the knowledge. The answers to the attitude and the preparedness items were also not satisfying. Lack of knowledge is one of the common reasons for not performing BLS. Periodical training program and refresher courses were the most recommended methods to increase the knowledge toward the BLS. CONCLUSION: It is evident from the current study that there is a lack of knowledge and preparedness toward BLS among most health care students. It is recommended to incorporate more BLS training and refresher courses in the health care college curricula.

Potential Efficacy of ß-Amyrin Targeting Mycobacterial Universal Stress Protein by In Vitro and In Silico Approach.

The emergence of drug resistance and the limited number of approved antitubercular drugs prompted identification and development of new antitubercular compounds to cure Tuberculosis (TB). In this work, an attempt was made to identify potential natural compounds that target mycobacterial proteins. Three plant extracts (A. aspera, C. gigantea and C. procera) were investigated. The ethyl acetate fraction of the aerial part of A. aspera and the flower ash of C. gigantea were found to be effective against M. tuberculosis H37Rv. Furthermore, the GC-MS analysis of the plant fractions confirmed the presence of active compounds in the extracts. The Mycobacterium target proteins, i.e., available PDB dataset proteins and proteins classified in virulence, detoxification, and adaptation, were investigated. A total of ten target proteins were shortlisted for further study, identified as follows: BpoC, RipA, MazF4, RipD, TB15.3, VapC15, VapC20, VapC21, TB31.7, and MazF9. Molecular docking studies showed that ß-amyrin interacted with most of these proteins and its highest binding affinity was observed with Mycobacterium Rv1636 (TB15.3) protein. The stability of the protein-ligand complex was assessed by molecular dynamic simulation, which confirmed that ß-amyrin most firmly interacted with Rv1636 protein. Rv1636 is a universal stress protein, which regulates Mycobacterium growth in different stress conditions and, thus, targeting Rv1636 makes M. tuberculosis vulnerable to host-derived stress conditions.

Edaravone and benidipine protect myocardial damage by regulating mitochondrial stress, apoptosis signalling and cardiac biomarkers against doxorubicin-induced cardiotoxicity.

Background: Doxorubicin (DOX) is a potential chemotherapeutic agent but its use is restricted due to cardiotoxicity. Edaravone is a potent-free radical scavenging agent used in cerebral ischaemia. Benidipine is a triple calcium channel blocker.Objective: We investigated the potential cardioprotective effects of edaravone and benidipine alone and their combination against DOX-induced cardiotoxicity. Cardiotoxicity was induced by administering six equal injections of DOX (2.5 mg/kg) on alternative days for 2 weeks.Result: DOX-treated group showed significant increase level of lipid peroxide and decrease in antioxidant status along with mitochondrial enzymatic activity. Cardiotoxity effect of DOX illustrated by significantly increased the cardiac biomarkers such as Cardiac troponin-I, Brain natriuretic peptide, Creatine kinase-MB in serum. Significant increased activation of TNF-α, Caspase-3 activity and myocardial infarct size in DOX-treated group. Histopathological evaluation also confirmed the DOX-induced cardiotoxicity. Pretreated with edaravone and benidipine was significantly attenuated level of thiobarbituric acid reactive substance, endogenous enzymes, mitochondrial enzyme activities and cardiac biomarkers. Furthermore, pretreated group showed decreased activation of TNF-α, Caspase-3 activity along with reduction in the myocardial infarct size. Histopathological evaluation also strengthened the above results.Conclusion: Taken together these results suggest that the pretreated with edaravone and benidipine have potential protective effect against DOX-induced cardiotoxicity.

Sacubitril and valsartan protect from experimental myocardial infarction by ameliorating oxidative damage in Wistar rats.

BACKGROUND: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin. OBJECTIVE: The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL). RESULT: Biochemical investigation revealed that SAC along with VAL significantly prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH) degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats. Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently, decreased infarction area (IA)and marked reduction in myofibril damage by SACand VAL further supported its protective benefits in MI. CONCLUSION: Taken together, the results suggest that inhibition of enzyme neprilysin alleviated the ISO induces myocardial damage mediated by its strong antioxidant potential.

Pitavastatin ameliorates myocardial damage by preventing inflammation and collagen deposition via reduced free radical generation in isoproterenol-induced cardiomyopathy.

Pitavastatin inhibits 3 hydroxy 3 methyl glutaryl coenzyme A (HMGCoA) reductase enzyme, preventing cholesterol synthesis along with elevating high density apolipoprotein A1 (Apo-A1). The present study was designed to evaluate cardioprotective potential of pitavastatin at 1 mg/kg/day and 3 mg/kg/day dose for 14 days in low dose isoproterenol (ISO) (5 mg/kg/day for 7 consecutive days) induced myocardial damage. ISO administration induced significant reduction in endogenous antioxidant enzymes like reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and raised thiobarbituric acid reactive substances (TBARS) indicating activated lipid peroxidation. Along with this, a significant increase in level of cardiac injury biomarkers vie, creatine kinase (CK-MB), lactate dehydrogenase (LDH), aspartate amino transferase (AST), tumor necrosis factor (TNF-α) and transforming growth factor (TGF-ß) as well as brain natriuretic peptide (BNP). Histological examination also revealed marked myocardial tissue damage in ISO treated rats. However, pretreatment with pitavastatin (3 mg/kg/day) significantly maintained nearly normal levels of cardiac biomarkers and oxidant antioxidant status as well as lipid peroxidation in ISO induced MI rats. Cardiac histological assessment and infarct size assessment also showed marked reduction in myocardial architecture alteration including infarct size as well as collagen deposition by pitavastatin that strongly supported biochemical findings. These observations strongly corroborate that pitavastatin prevents myocardial damages via up regulation of endogenous oxidants along with its hypocholesterolemic activity.

Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors.

A new series of benzimidazole linked pyrazole derivatives were synthesized by cyclocondensation reaction through one-pot multicomponent reaction in absolute ethanol. All the synthesized compounds were tested for their in vitro anticancer activities on five human cancer cell lines including MCF-7, HaCaT, MDA-MB231, A549 and HepG2. EGFR receptor inhibitory activities were carried out for all the compounds. Majority of the compounds showed potent antiproliferative activity against the tested cancer cell lines. Compound 5a showed the most effective activity against the lungs cancer cell lines (IC50 = 2.2 µM) and EGFR binding (IC50 = 0.97 µM) affinity as compared to other members of the series. Compound 5a inhibited growth of A549 cancer cells by inducing a strong G2/M phase arrest. In addition, same compound inhibited growth of A549 cancer cells by inducing apoptosis. In molecular docking studies compound 5a was bound to the active pocket of the EGFR (PDB 1M17) with five key hydrogen bonds and two π-π interaction with binding energies ΔG = -34.581 Kcal/mol.

Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy.

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25 mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia ((§§§)p < 0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.

Benidipine prevents oxidative stress, inflammatory changes and apoptosis related myofibril damage in isoproterenol-induced myocardial infarction in rats.

OBJECTIVE: The effects of benidipine on oxidative stress and myocardial apoptosis were assessed in isoproterenol (ISO)-induced myocardial infarction (MI) in wistar rats. MATERIALS AND METHOD: Animals were pretreated with benidipine (1, 3, 10 µg/kg/day Body weight) intravenously for a period of 28 days. After pretreatment, ISO (85 mg/kg Body weight, subcutaneous) was injected in rats at an interval of 24 h to induce MI. Myocardial oxidative stress, cardiac biomarkers, apoptosis, inflammatory mediators, and ultrastructural architecture of the cardiac tissue were assessed in ISO-induced MI in rats. RESULT: Significant variation in the level of TBA, antioxidant enzymes (GSH, CAT, SOD, GPx, GRx, GST) in myocardium, cardiac biomarkers (CK-MB, LDH) in serum, Caspase-3, C-reactive protein (CRP), and alteration in ultrastructural architecture of cardiac tissue confirmed the cardiotoxicity induced by ISO. Pretreatment with benidipine preserved the lipid peroxide and antioxidant enzymes, and furthermore showed maintained levels of myocardial biomarker, CRP and caspase-3. Ultrastructure architecture of cardiac tissue was also found to be well preserved. CONCLUSION: The present study suggested cardioprotective effect of benidipine which may possibly be due to its antioxidant activity and antiapoptotic nature.

Validating the temporal performance of genetic biomarkers in an animal model of recurrence/ non-recurrence myocardial infarction persuades by bioinformatics tools.

With a global towering prevalence of index acute myocardial infarction (nonrecurrent MI, NR-MI), a high incidence of recurrent MI (R-MI) has emerged in recent decades. Despite the extensive occurrence, the promising predictors of R-MI have been elusive within the cohort of survivors. This study investigates and validates the involvement of distinct gene expressions in R-MI and NR-MI. Bioinformatics tools were used to identify DEGs from the GEO dataset, functional annotation, pathway enrichment analysis, and the PPI network analysis to find hub genes. The validation of proposed genes was conceded by qRT-PCR and Western Blot analysis in experimentally induced NR-MI and R-MI models on a temporal basis. The temporal findings based on RT-PCR consequences reveal a significant and constant upregulation of the UBE2N in the NR-MI model out of the proposed three DEGs (UBE2N, UBB, and TMEM189), while no expression was reported in the R-MI model. Additionally, the proteomics study proposed five DEGs (IL2RB, NKG7, GZMH, CXCR6, and GZMK) for the R-MI model since IL2RB was spotted for significant and persistent downregulation with different time points. Further, Western Blot analysis validated these target genes' expressions temporally. I/R-induced NR-MI and R-MI models were confirmed by the biochemical parameters (CKMB, LDH, cTnI, serum nitrite/nitrate concentration, and inflammatory cytokines) and histological assessments of myocardial tissue. These results underscore the importance of understanding genetic mechanisms underlying MI and highlight the potential of UBE2N and IL2RB as biomarkers for non-recurrent and recurrent MI, respectively.

Integrative experimental validation of concomitant miRNAs and transcription factors with differentially expressed genes in acute myocardial infarction.

Identification of concomitant miRNAs and transcription factors (TFs) with differential expression (DEGs) in MI is crucial for understanding holistic gene regulation, identifying key regulators, and precision in biomarker and therapeutic target discovery. We performed a comprehensive analysis using Affymetrix microarray data, advanced bioinformatic tools, and experimental validation to explore potential biomarkers associated with human pathology. The search strategy includes the identification of the GSE83500 dataset, comprising gene expression profiles from aortic wall punch biopsies of MI and non-MI patients, which were used in the present study. The analysis identified nine distinct genes exhibiting DEGs within the realm of MI. miRNA-gene/TF and TF-gene/miRNA regulatory relations were mapped to retrieve interacting hub genes to acquire an MI miRNA-TF co-regulatory network. Furthermore, an animal model of I/R-induced MI confirmed the involved gene based on quantitative RT-PCR and Western blot analysis. The consequences of the bioinformatic tool substantiate the inference regarding the presence of three key hub genes (UBE2N, TMEM106B, and CXADR), a central miRNA (hsa-miR-124-3p), and sixteen TFs. Animal studies support the involvement of predicted genes in the I/R-induced myocardial infarction assessed by RT-PCR and Western blotting. Thus, the final consequences suggest the involvement of promising molecular pathways regulated by TF (p53/NF-κB1), miRNA (hsa-miR-124-3p), and hub gene (UBE2N), which may play a key role in the pathogenesis of MI.

Self-Emulsifying Drug Delivery System for Enhanced Oral Delivery of Tenofovir: Formulation, Physicochemical Characterization, and Bioavailability Assessment.

Tenofovir (TNF) is a common component of many antiretroviral therapy regimens, but it is associated with poor membrane permeability and low oral bioavailability. To improve its oral bioavailability and membrane permeability, a self-emulsifying drug delivery system (SEDDS) was developed and characterized, and its relative bioavailability was compared to the marketed tablets (Tenof). Based on solubility and ternary phase diagram analysis, eucalyptus oil was selected as an oil phase, Kolliphor EL, and Kollisolv MCT 70 were chosen as surfactant and cosurfactant, respectively, while glycerol was used as cosolvent in surfactant mixture. Optimized SEDDS formulation F6 showed an oil droplet size of 98.82 nm and zeta potential of -13.03 mV, indicating the high stability of oil droplets. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy characterization studies were also carried out to assess the amorphous and morphological states of the drug in the prepared SEDDS formulation. The in vitro dissolution profile of SEDDS shows the rapid release of the drug. SEDDS F6 demonstrates a higher drug permeability than the plain TNF and TNF-marketed tablets (Tenof). A pharmacokinetic study in rats revealed that SEDDS F6 showed significantly higher Cmax and AUC0-t than the marketed tablets and pure drug suspension. In addition, the relative bioavailability of SEDDS formulation dramatically improved by 21.53-fold compared to marketed tablets and 66.27-fold compared to pure drugs. These findings show that SEDDS composed of eucalyptus oil, glycerol, Kolliphor EL, and Kollisolv MCT 70 could be a useful tool for enhancing physiochemical properties and oral TNF absorption. Therefore, SEDDS has shown promise in improving the oral bioavailability of poorly water-soluble drugs.

Ganoderma lucidum: Insight into antimicrobial and antioxidant properties with development of secondary metabolites.

Ganoderma lucidum is a versatile mushroom. Polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicinal mushrooms since ancient times. They are currently used as nutraceuticals and functional foods. G. lucidum extracts and their bioactive compounds have been used as an alternative to antioxidants and antimicrobial agents. Secondary metabolites with many medicinal properties make it a possible substitute that could be applied as immunomodulatory, anticancer, antimicrobial, anti-oxidant, anti-inflammatory, and anti-diabetic. The miraculous properties of secondary metabolites fascinate researchers for their development and production. Recent studies have paid close attention to the different physical, genetic, biochemical, and nutritional parameters that potentiate the production of secondary metabolites. This review is an effort to collect biologically active constituents from G. lucidum that reveal potential actions against diseases with the latest improvement in a novel technique to get maximum production of secondary metabolites. Studies are going ahead to determine the efficacy of numerous compounds and assess the valuable properties achieved by G. lucidum in favor of antimicrobial and antioxidant outcomes.

Comparative Efficacy of Levosimendan, Ramipril, and Sacubitril/ Valsartan in Isoproterenol-induced Experimental Heart Failure: A Hemodynamic and Molecular Approach.

OBJECTIVE: Cardiac ischemia-related myocardial damage has been considered a major reason for heart failure. We aimed to investigate the role of levosimendan (LEVO) in comparison to ramipril and sacubitril/valsartan (Sac/Val) in preventing damage associated with isoproterenol (ISO) induced myocardial infarction. METHODS: Myocardial infarction was induced by injecting subcutaneous isoproterenol (5 mg/kg once for 7 consecutive days) to establish an experimental heart failure model. Simultaneously, LEVO (1 mg/kg/day), ramipril (3mg/kg/day) and Sac/Val (68 mg/kg/day) suspension were administered orally for four weeks. RESULTS: We observed a significant correlation between ISO-induced ischemia with cardiac remodeling and alterations in myocardial architecture. LEVO, ramipril, and Sac/Val significantly prevented lipid peroxidation and damaged antioxidant enzymes like superoxide dismutase, catalase, glutathione and thioredoxin reductase. We also observed their ameliorative effects in myocardium's cardiac hypertrophy, evidenced by reduced heart weight to body weight ratio and transforming growth factor ß related collagen deposition. LEVO, ramipril, and Sac/Val also maintained cardiac biomarkers like lactate dehydrogenase, creatine kinase-MB, brain natriuretic peptide and cardiac Troponin-I, indicating reduced myocardial damage that was further demonstrated by histopathological examination. Decreased sarcoplasmic endoplasmic reticulum Ca2+ATPase2a and sodium-calcium exchanger-1 protein depletion after LEVO, ramipril, and Sac/Val administration indicated improved Ca2+ homeostasis during myocardial contractility. CONCLUSION: Our findings suggest that LEVO has comparable effects to ramipril, and Sac/Val in preventing myocardial damage via balancing oxidant-antioxidant system, decreased collagen deposition, reduced myocardial stress as well as improved Ca2+ homeostasis during myocardial contractility.

Preliminary investigation on impact of intergenerational treatment of resveratrol endorses the development of 'super-pups'.

BACKGROUND: Redox biology balances free radical generation and scavenging systems, whereas an imbalanced cellular redox can hasten the onset of various diseases and be regarded as a Pandora's box of ailments. The current study aims to assess the pathophysiological impact of intergenerational resveratrol treatment on diabetes-related cognitive and cardio-renal disorders. MATERIAL AND METHOD: Diabetic rats of the first, second, and third generations were subjected to an intergenerational treatment of resveratrol (20 mg/kg/p.o./day) for 5 months. During this period, the second generation of animals (pups of the first generation) was produced. After the adulthood of second-generation rats, they used to produce third-generation rats. The rats of each generation were evaluated for physiological parameters (BMI, litter size, and life expectancy) and the pathological impact of streptozotocin (55 mg/kg/i.p.), cognitive dysfunctions, and cardio-renal injury. RESULTS: The intergenerational treatment of resveratrol significantly reduced litter size and improved anthropometric parameters, life expectancy, and blood glucose levels in diabetic animals. Resveratrol treatment ameliorates oxidative stress as measured by increased serum nitrite/nitrate concentrations, SOD activity, reduced glutathione concentrations, total serum antioxidant capacity, and diminished serum TBARS level in diabetic animals. Furthermore, diabetic rats receiving intergenerational resveratrol treatment showed improved cognitive behaviour and cardio-renal functionality when compared to the disease control group. CONCLUSION: The intergenerational treatment of resveratrol improved the physiological traits and vital abilities of the heart, kidney, and brain, which endorse its antioxidant potential. Surprisingly, resveratrol treatment increases the second and third generations' resistance to neurobehavioral changes, diabetes, and -associated cardio-renal dysfunction, implying that these generations are "super-pups."

Current understanding of structural and molecular changes in diabetic cardiomyopathy.

Diabetic Mellitus has been characterized as the most prevalent disease throughout the globe associated with the serious morbidity and mortality of vital organs. Cardiomyopathy is the major leading complication of diabetes and within this, myocardial dysfunction or failure is the leading cause of the emergency hospital admission. The review is aimed to comprehend the perspectives associated with diabetes-induced cardiovascular complications. The data was collected from several electronic databases such as Google Scholar, Science Direct, ACS publication, PubMed, Springer, etc. using the keywords such as diabetes and its associated complication, the prevalence of diabetes, the anatomical and physiological mechanism of diabetes-induced cardiomyopathy, the molecular mechanism of diabetes-induced cardiomyopathy, oxidative stress, and inflammatory stress, etc. The collected scientific data was screened by different experts based on the inclusion and exclusion criteria of the study. This review findings revealed that diabetes is associated with inefficient substrate utilization, inability to increase glucose metabolism and advanced glycation end products within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity, and initially subclinical cardiac dysfunction and finally in overt heart failure. Furthermore, several factors such as hypertension, overexpression of renin angiotensin system, hypertrophic obesity, etc. have been seen as majorly associated with cardiomyopathy. The molecular examination showed biochemical disability and generation of the varieties of free radicals and inflammatory cytokines and becomes are the substantial causes of cardiomyopathy. This review provides a better understanding of the involved pathophysiology and offers an open platform for discussing and targeting therapy in alleviating diabetes-induced early heart failure or cardiomyopathy.

Amelioration of Cancer Employing Chitosan, Its Derivatives, and Chitosan-Based Nanoparticles: Recent Updates.

The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review.

Resveratrol-Loaded Chia Seed Oil-Based Nanogel as an Anti-Inflammatory in Adjuvant-Induced Arthritis.

Natural anti-inflammatory nutraceuticals may be useful in preventing rheumatoid arthritis from worsening. Resveratrol (RV) and chia seed oil, having antioxidant potential, can assist in avoiding oxidative stress-related disorders. This investigation developed and evaluated resveratrol-loaded chia seed oil-based nanoemulsion (NE) gel formulations through in vitro and in vivo studies. The physical stability and in vitro drug permeability of the chosen formulations (NE1 to NE10) were studied. The optimized RV-loaded nanoemulsion (NE2) had droplets with an average size of 37.48 nm that were homogeneous in shape and had a zeta potential of -18 mV. RV-NE2, with a permeability of 98.21 ± 4.32 µg/cm2/h, was gelled with 1% carbopol-940P. A 28-day anti-arthritic assessment (body weight, paw edema, and levels of pro-inflammatory mediators including TNF-α, IL-6, IL-1ß, and COX-2) following topical administration of RV-NE2 gel showed significant reversal of arthritic symptoms in arthritic Wistar rats induced by Freund's complete adjuvant injection. Therefore, RV-NE2 gel demonstrated the potential to achieve local therapeutic benefits in inflammatory arthritic conditions due to its increased topical bioavailability and balancing of pro-inflammatory mediators.

Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB).

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Impact of Clinical Pharmacist Running Anticoagulation Clinic in Saudi Arabia.

Despite the effectiveness of warfarin in extended anticoagulation, its narrow therapeutic index requires frequent dose adjustments and careful patient monitoring. Thus, we aimed to evaluate the outcomes of clinical pharmacists' intervention in warfarin therapy management in terms of International Normalized Ratio (INR) control, reduction of bleeding, and hospitalization in a tertiary care hospital. An observational retrospective cohort study was conducted on 96 patients taking warfarin therapy in a clinical pharmacist-led anticoagulation clinic. We observed that 39.6% of patients required dose adjustments at their first and second visits. However, dose adjustments during the third, fourth, and fifth weeks were required at 31.1%, 20.8%, and 4.2%, respectively, to achieve INR levels. We also observed that 36.46% of the patients attained the target INR at baseline, which was increased over the first week to the fifth week to 57.29%, 61.46%, 61.46%, 68.75%, and 85.42%, respectively. No one reported the ADR between the third and fifth weeks. Based on our findings, the study strongly suggests that pharmacists' interventions can improve the health-related quality of life of patients undergoing warfarin therapy. Thus, competent pharmacy personnel must be a priority in both usual patient care and critical care among primary care networks.