Molecular interplay between phytoconstituents of Ficus Racemosa and neurodegenerative diseases.

Neurodegenerative diseases (NDs) are a significant global health concern, primarily affecting middle and older populations. Recently, there has been growing interest in herbal therapeutics as a potential approach to address diverse neuropathological conditions. Despite the widespread prevalence of NDs, limited phytochemical has been reported for their promising therapeutic potential with distinct underlying mechanisms. Additionally, the intricate molecular pathways influenced by herbal phytoconstituents, particularly in neurodegenerative disorders, are also not well documented. This report explores the phytoconstituents of Ficus racemosa (F. racemosa), an unfamiliar plant of the Moraceae family, for their potential interactions with pathological pathways of NDs. The influential phytoconstituents of F. racemosa, including polyphenols, glycosides, terpenoids, and furocoumarin, have been reported for targeting diverse pathological states. We proposed the most convincing molecular interplay between leading phytoconstituents and detrimental signalling cascades. However, extensive research is required to thoroughly understand the phytochemical persuaded intricate molecular pathway. The comprehensive evidence strongly suggests that F. racemosa and its natural compounds could be valuable in treating NDs. This points towards an exciting path for future research and the development of potential treatments based on a molecular level.

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.

Harnessing Folate-Functionalized Nasal Delivery of Dox-Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis.

The aim of the present study is to develop Doxorubicin-Erlotinib nanoparticles (Dox-Erlo NPs) and folate-armored Dox-Erlo-NP conjugates for targeting glioma cancer. Glioma is one of the most common progressive cancerous growths originating from brain glial cells. However, the blood-brain barrier (BBB) is only semi-permeable and is highly selective as to which compounds are let through; designing compounds that overcome this constraint is therefore a major challenge in the development of pharmaceutical agents. We demonstrate that the NP conjugates studied in this paper may ameliorate the BBB penetration and enrich the drug concentration in the target bypassing the BBB. NPs were prepared using a biopolymer with a double-emulsion solvent evaporation technique and functionalized with folic acid for site-specific targeting. Dox-Erlo NPs and Dox-Erlo-NP conjugates were extensively characterized in vitro for various parameters. Dox-Erlo NPs and Dox-Erlo-NP conjugates incurred a z-average of 95.35 ± 10.25 nm and 110.12 ± 9.2 nm, respectively. The zeta potentials of the Dox-Erlo NPs and Dox-Erlo-NP conjugates were observed at -18.1 mV and -25.1 mV, respectively. A TEM image has shown that the NPs were well-dispersed, uniform, de-aggregated, and consistent. A hemolytic assay confirmed hemocompatibility with the developed formulation and that it can be safely administered. Dox-Erlo-NP conjugates significantly reduced the number of viable cells to 24.66 ± 2.08% and 32.33 ± 2.51% in U87 and C6 cells, respectively, and IC50 values of 3.064 µM and 3.350 µM in U87 and C6 cells were reported after 24 h, respectively. A biodistribution study revealed that a significant concentration of Dox and Erlo were estimated in the brain relative to drug suspension. Dox-Erlo-NP conjugates were also stable for three months. The findings suggest that the developed Dox-Erlo-NP conjugates may be a promising agent for administration in glioma therapy.

Dysbiosis versus diabesity: Pathological signaling and promising therapeutic strategies.

A healthy life depends on the inseparable relationship between a host and the gut microbiota. A healthy gut microbiota regulates intestinal integrity, whereas an unbalanced gut microbiota contributes to junctional remodeling and leads to dysbiosis. Bacterial infiltration and dysbiosis are reported to activate a series of pathological cascades that trigger metabolic abnormalities, including diabesity. Conversely, recent studies revealed that the incidence of dysbiosis itself is fuelled by diabesity. In this review, we highlight the molecular aspects of multifaceted pathological signaling between dysbiosis and diabetes that could pave the way for new drug discovery. Moreover, to reinstate the gut microbiota and restrict the epidemic of dysbiosis and diabesity, we also scrutinize a promising therapeutic strategy that can challenge the pathological interlink.

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.

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."

Levosimendan: mechanistic insight and its diverse future aspects in cardiac care.

Inotropic agents are generally recommended to use in patients with acute decompensated heart failure (HF) with reduced ejection fraction (HFrEF) concurrent to end-organ dysfunction. However, due to certain pharmacological limitations like developing life threatening arrhythmia and tolerance, cannot be employed as much as needed. Meanwhile, Calcium ion (Ca2+) sensitisers exhibits their inotropic action by increasing the sensitivity of the cardiomyocyte to intracellular Ca2+ ion and have been reported as emerging therapeutic alternative in HF cases. Levosimendan (LEVO) is an inodilator and with its unique pharmacology justifying its use in a wide range of cardiac alterations in HF particularly in undergoing cardiac surgery. It is also reported to be better than classical inotropes in maintaining cardiac mechanical efficacy and reducing congestion in acute HF with hypotension. This review paper was designed to compile various evidence about basic pharmacology and potential clinical aspects of LEVO in cardiac surgery and other HF associated alterations. This will benefit directly to the researcher in initiating research and to fill the gaps in the area of thrust.

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.

Impact of polycystic ovary syndrome on quality of life of women in correlation to age, basal metabolic index, education and marriage.

Polycystic ovary syndrome (PCOS) is the major endocrine related disorder in young age women. Physical appearance, menstrual irregularity as well as infertility are considered as a sole cause of mental distress affecting health-related quality of life (HRQOL). This prospective case-control study was conducted among 100 PCOS and 200 healthy control cases attending tertiary care set up of AIIMS, Patna during year 2017 and 2018. Pre-validated questionnaires like Short Form Health survey-36 were used for evaluating impact of PCOS in women. Multivariate analysis was applied for statistical analysis. In PCOS cases, socioeconomic status was comparable in comparison to healthy control. But, PCOS cases showed significantly decreased HRQOL. The higher age of menarche, irregular/delayed menstrual history, absence of child, were significantly altered in PCOS cases than control. Number of child, frequency of pregnancy, and miscarriage were also observed higher in PCOS cases. Furthermore, in various category of age, BMI, educational status and marital status, significant differences were observed in the different domain of SF-36 between PCOS and healthy control. Altogether, increased BMI, menstrual irregularities, educational status and marital status play a major role in altering HRQOL in PCOS cases and psychological care must be given during patient care.

Evaluation of Antibiotic Prescribing Practices and Antimicrobial Sensitivity Patterns in Urinary Tract Related Infectious Diseases in Pediatric Patients.

Complications of urinary tract infections (UTIs) like kidney failure and septicaemia develop once infections spread from the upper urinary tract to other parts of the body by haematogenous dissemination and they pose great health and economic burden to the countries. This retrospective study was conducted among 132 patients with bacterial UTIs in the inpatient department of tertiary care hospital in Abha, Saudi Arabia. During the study period, Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia) along with other 15 different bacteria were isolated. A significant difference (P < 0.05) was observed between the male and female children population in different age groups. We observed fever (84.09%) as a major symptom (P < 0.05), and seizure (9%) was reported as a major concomitant condition among UTI cases. Around 31.82% of E. coli was found to be the most common uropathogens in pediatric cases followed by 25% in K. pneumoniae. E. coli was observed to be more susceptible (92.86%) to amikacin, ceftriaxone, levofloxacin, ertapenem, gentamycin, meropenem, piperacillin-tazobactam, tigecycline, and ceftazidime. However, meropenem, tigecycline, and amikacin were observed to be effective in 100% of cases of K. pneumoniae. Meanwhile, cephalosporins were the most commonly prescribed drug category among different classes of drugs. Almost 99% of pediatric cases, based on their age, were admitted to the ward, and drugs were administered intravenously. We concluded that microbiology laboratory evidence on the causative organisms and choice of treatment together allows tailoring appropriate treatment regimens in conjunction with clinical experiences.

Potential facilitators and barriers to adopting standard treatment guidelines in clinical practice.

Purpose The purpose of this paper is to assess medicines information sources accessed by clinicians, if sources differed in theory and practice and to find out the barriers and facilitators to effective guideline adoption. Design/methodology/approach In all, 183 doctors were surveyed. Barriers and facilitators were classified as: communication; potential adopters; innovation; organization characteristics and environmental/social/economic context. Findings Most of the clinicians accessed multiple information sources including standard treatment guidelines, but also consulted seniors/colleagues in practice. The top three factors influencing clinical practice guideline adoption were innovation characteristics, environmental context and individual characteristics. The respondents differed in the following areas: concerns about flexibility offered by the guideline; denying patients' individuality; professional autonomy; insights into gaps in current practice and evidence-based practice; changing practices with little or no benefit. Barriers included negative staff attitudes/beliefs, guideline integration into organizational structures/processes, time/resource constraints. Fearing third parties (government and insurance companies) restricting medicines reimbursement and poor liability protection offered by the guidelines emerged as the barriers. Facilitators include aligning organizational structures/processes with the innovation; providing leadership support to guide diffusion; increasing awareness and enabling early innovation during pre/in-service training, with regular feedback on outcomes and use. Practical implications Guideline adoption in clinical practice is partly within doctors' control. There are other key prevailing factors in the local context such as environmental, social context, professional and organizational culture affecting its adoption. Organizational policy and accreditation standards necessitating adherence can serve as a driver. Originality/value This survey among clinicians, despite limitations, gives helpful insights. While favourable attitudes may be helpful, clinical adoption could be improved more effectively by targeting barriers.

Frontline worker perceptions of medication safety in India.

BACKGROUND: To explore interprofessionals' perceptions about patient safety, particularly medication safety and associated factors and barriers. METHODS: A total of 389 respondents were recruited using convenience sample in the cross sectional survey. RESULTS: Medication safety was perceived as somewhat safe (60%). One-third of respondents witnessed 3-4 or more medication errors (MEs) within the past 1 year. Out of that, one quarter were reportedly, sentinel events. More sentinel events were witnessed in public hospitals and solo practice clinics compared with corporate hospitals and nursing homes (p < 0.02). No difference was observed in the occurrence of sentinel events in accredited and nonaccredited facilities (p = 0.30). Younger respondents witnessed more MEs, whereas accredited hospitals (mostly corporate hospitals) witnessed significantly fewer MEs and graded overall safety as 'better'. However, most MEs go unreported particularly in solo practice clinics (88%) followed by nursing homes (67%), public hospitals (54%), and corporate hospitals (42%). Error identification and subsequent disclosure was inhibited by several system factors: fear of punitive action and lack of reporting systems. General surgical (46%), medical (42%), and paediatric units (36%), were the most error-prone places. Documentation diverted all healthcare workers from direct patient care. Many doctors and pharmacists from nursing homes, solo clinics and public hospitals reported working overtime. Staff shortages and poor training were overwhelming concerns to all healthcare workers and in public hospitals. Solo clinics and nursing homes perceived more barriers; lack of reporting systems, standard protocol, and resources for patient safety and unfamiliarity with prescribed medications was their overwhelming concern. Other factors threatening MEs were a lack of team approach and openness in interdisciplinary communications, illegible medical orders, and medicines prescribed by brand names. CONCLUSIONS: Immediate interventions to improve medication safety include enforcement of legible/printed medical orders in generic names, workforce development, developing standard protocols, and a corresponding change in organizational culture. Accreditation can serve as a driver for improving patient safety.

Critical appraisal of serum phenytoin variation with patient characteristics in a North Indian population.

CONTEXT: Phenytoin (PHT) is one of the frontrunner drugs used as monotherapy in the management of epilepsy. It is also one of the most common drugs causing adverse drug reactions (ADRs). The aim of this study was to study the relationship between serum PHT levels and the age, gender, dosage and genetic polymorphisms in a North Indian population. This knowledge will help in devising drug dosage schedules in various sub-groups of patients as well as in reducing its ADRs. MATERIALS AND METHODS: A retrospective analysis of data of 6224 patients from 1998 to 2009 receiving PHT alone for greater than (>) 4 weeks was performed. Patients suspected of being non-compliant, being overdosed or having a hepatic or renal disorder were excluded from the study. Two thousand eight hundred and eighty-eight patients fulfilling the inclusion criteria were divided into three groups: children (1-18 years), adults (19-60 years) and elderly (>60 years). RESULTS: There was a male preponderance (80%) in all the groups. A significant difference was found in the mean dose between children and adults as well as between children and elderly (P = 0.00). Also, there was a significant difference in the mean concentration and dose ratio between children and adults (P = 0.00). However, a negative correlation was observed between the daily dose and dose ratio (r = -0.36, P = 0.00) that was highest (r = -0.58, P = 0.00) in the elderly. There was a significant gender difference in the mean dose in both children (P = 0.03) and adults (P = 0.00), whereas the mean concentration differed in adults only. Every fifth patient was an intermediate metabolizer (IM) (CYP2C9FNx011/FNx013) and showed higher steady state drug levels (>17 mg/L) compared with extensive metabolizers (EMs) (<12 mg/L). The genetic difference between IM and EM was more prevalent in the dose ratio at maintenance dose, with a mean ± SD of 4.041 ± 1.288 mg/L/mg/kg in nine patients carrying the CYP2C9FNx011/FNx013 genotype compared with 2.145 ± 0.817 mg/L/mg/kg in 26 patients carrying the CYP2C9FNx011/FNx011 genotype (P = 0.00). CONCLUSION: North Indian female children and male adults frequently attain a higher serum concentration with the same dose when compared to the other groups. Absence of poor metabolizers may be responsible for a lower number of cases exhibiting toxicity in our population; however, this needs elucidation in a larger number of patients.

Emblica officinalis exerts antihypertensive effect in a rat model of DOCA-salt-induced hypertension: role of (p) eNOS, NO and oxidative stress.

Emblica officinalis (EO) has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone acetate/1% NaCl high salt (DOCA/HS)-induced hypertension. We determined whether hydroalcoholic lyophilized extract of EO may influence DOCA/HS-induced hypertension by modulating activity of (p) eNOS and endogenous antioxidants. Hypertension was induced in rats by DOCA-salt (20 mg/kg, s.c.) twice weekly for 5 weeks and replacing drinking water with 1% NaCl solution. These rats received cotreatment of different doses of EO (75, 150 and 300 mg/kg/day) for 5 weeks. EO significantly decreased arterial blood pressure and heart rate along with cardiac and renal hypertrophy in a dose-dependent fashion as compared to DOCA control rats. Increased TBARS and decreased endogenous antioxidants including GSH, SOD and GSHPx activity in serum, heart and kidney tissues of hypertensive rats were also normalized. Furthermore, this antihypertensive activity of EO was also linked with increased serum NO, K(+) levels and decreased Na(+) levels. Moreover, EO robustly increased activated eNOS expression in heart. Our results demonstrate that EO reduces oxidative stress, prevents development and progression of hypertension as well as cardiac and renal hypertrophy in DOCA/HS-induced hypertension via modulation of activated eNOS, endogenous antioxidants, serum NO and electrolyte levels.