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Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. Theexisting study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90days were also observed. In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

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Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. Theexisting study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90days were also observed. In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

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Current developments and advancements of 3-dimensional printing in personalized medication and drug screening.

3-Dimensional printing (3DP) is an additive manufacturing (AM) technique that is expanding quickly because of its low cost and excellent efficiency. The 3D printing industry grew by 19.5 % in 2021 in spite of the COVID-19 epidemic, and by 2026, the worldwide market is expected to be valued up to 37.2 billion US dollars. Science Direct, Scopus, MEDLINE, EMBASE, PubMed, DOAJ, and other academic databases provide evidence of the increased interest in 3DP technology and innovative drug delivery approaches in recent times. In this review four main 3DP technologies that are appropriate for pharmaceutical applications: extrusion-based, powder-based, liquid-based, and sheet lamination-based systems are discussed. This study is focused on certain 3DP technologies that may be used to create dosage forms, pharmaceutical goods, and other items with broad regulatory acceptance and technological viability for use in commercial manufacturing. It also discusses pharmaceutical applications of 3DP in drug delivery and drug screening. The pharmaceutical sector has seen the prospect of 3D printing in risk assessment, medical personalisation, and the manufacture of complicated dose formulas at a reasonable cost. AM has great promise to revolutionise the manufacturing and use of medicines, especially in the field of personalized medicine. The need to understand more about the potential applications of 3DP in medical and pharmacological contexts has grown over time.

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The potential antibacterial effects of tea polyphenols.

The current review of tea and its parts is focused on the antibacterial properties, considering the possible applications and modes of action against bacterial illnesses. It shows the backdrop of antibiotic resistance and the hugedemand for antibacterial treatments out there. From the interactions with bacterial components, the theory presented that tea polyphenols are antibacterial and therefore would be a substitute or supplementary therapy to the usual antibiotics. The study highlighted the role of tea polyphenols as potential antibacterial compounds that may interact with various bacterial components and different polyphenolic compounds occurring in tea. Future research directions may be directed toward testing more plant-based sources for antibacterial properties, invivo validation of the studies, and possible synergistic effects with classical antibiotics. By addressing the controversies and disagreements involved, the present understanding of the topic of tea's antibacterial properties and enable the entry of new ways for fighting microorganisms resistant to antibiotics. In conclusion, this review adds to the growing body of evidence regarding the antimicrobial properties of tea and emphasizes the need for further studies that will allow the full exploitation of its therapeutic potential for countering the rising problem of antibiotic resistance in healthcare.

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Effect of a polyherbal Unani formulation on left ventricular diastolic dysfunction in hypertensive patients- a randomized single blind placebo controlled clinical trial.

Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function. This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15days to assess both subjective and objective parameters in all participants. The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control. The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.

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Molecular pathogenesis of microsatellite instability-high early-stage colorectal adenocarcinoma in India.

The prevalence of microsatellite instability (MSI) subtype among all colon cancers in India is about 30 %, approximately two times more than that of western population suggesting different molecular pathogeneses. A NanoString analysis-based Pan cancer differential expression (DE) profile was determined in a primary cohort of early-stage CRC (tumor=10, normal=7), and correlated against MSI status. Using RT-PCR, tumor-specific DE genes were validated in another cohort of MSI-high CRC (n=15). Among the most differentially expressed genes, AXIN2, ETV4, and RNF43 were tumor cell-specific signals, while a set of genes including COL11A1, COMP, INHBA, SPP1, MMP3, TLR2, and others were immune cell-specific signals, that had a differential expression between MSI and MSS groups. When overlapped with The Cancer Genome Atlas (TCGA) studies using the Tumor immune estimation resource tool (TIMER), and protein-protein interaction analysis by STRING.db, these genes were segregated to representative tumor cells and immune cells. On validation, the tumor-specific gene signals were inversely associated with TLR4 expression. The differential expression distribution of AXIN2, ETV4, and RNF43 among tumor and immune cells, suggests more than one pathological subset in the MSI-H subgroup of early-stage CRC in the Indian population.

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The synergy of artificial intelligence and personalized medicine for the enhanced diagnosis, treatment, and prevention of disease.

The completion of the Human Genome Project in 2003 marked the beginning of a transformative era in medicine. This milestone laid the foundation for personalized medicine, an innovative approach that customizes healthcare treatments. Central to the advancement of personalized medicine is the understanding of genetic variations and their impact on drug responses. The integration of artificial intelligence (AI) into drug response trials has been pivotal in this domain. These technologies excel in handling large-scale genomic datasets and patient histories, significantly improving diagnostic accuracy, disease prediction and drug discovery. They are particularly effective in addressing complex diseases such as cancer and genetic disorders. Furthermore, the advent of wearable technology, when combined with AI, propels personalized medicine forward by offering real-time health monitoring, which is crucial for early disease detection and management. The integration of AI into personalized medicine represents a significant advancement in healthcare, promising more accurate diagnoses, effective treatment plans and innovative drug discoveries. As technology continues to evolve, the role of AI in enhancing personalized medicine and transforming the healthcare landscape is expected to grow exponentially. This synergy between AI and healthcare holds great promise for the future, potentially revolutionizing the way healthcare is delivered and experienced.

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Clinical and pharmacogenetic features of patients with upper gastrointestinal lesions at a multidisciplinary hospital: the role of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications, buttheir use can be associated with a number of adverse reactions, including upper gastrointestinal lesions. The aim of the study was to identify clinical and pharmacogenetic factors associated with upper gastrointestinal lesions, including those linked to NSAIDs, in patients at a multidisciplinary hospital. The study included 92 patients (mean age 59.4±16.5 years; 47 women), who underwent esophagogastroduodenoscopy during inpatient treatment. Patients' intake of NSAIDs and gastroprotectors during the year before hospitalization was considered. Demographic, clinical, laboratory data of patients were compared between groups, including genotyping for CYP2C9*2 rs179985, CYP2C9*3 rs1057910, CYP2C8*3 rs11572080, CYP2C8*3 rs10509681, PTGS-1 rs10306135, PTGS-1 rs12353214, and PTGS-2 rs20417 using real-time PCR. In NSAIDs+ patients, PTGS1 rs10306135 AT+TT genotypes increased the chance of developing gastrointestinal complications by 5.4 times (95 % CI=1.30-22.27). In total sample, smoking (OR=3.12, 95 % CI=1.15-8.46), and alcohol intake (OR=4.09, 95 % CI=1.05-15.87) increased odds of gastrointestinal damage. In NSAIDs+ patients omeprazole, famotidine and both famotidine and omeprazole during the last year were as ineffective as not taking gastroprotectors; in total sample famotidine (OR=0.19, 95 % CI=0.04-0.93) and two gastroprotectors (OR=0.13, 95 % CI=0.02-0.75) reduced the chance of upper gastrointestinal lesions. Pharmacogenetic features of patients may significantly contribute to the development NSAIDs-induced upper gastrointestinal injuries.

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Helicobacter pylori eradication therapy for children.

The research aims to investigate the effect of vitamin D supplementation on the efficacy of Helicobacter pylori eradication therapy and to find new drug combinations for the eradication of the bacterium. A total of 128 children participated in the research. They were distributed under the following criteria: group A were children who tested positive for H.pylori and were treated with the standard so-called triple therapy including vitamin D; group B were children who tested positive for H.pylori and received the standard triple therapy without including vitamin D in the treatment; and group C were children who tested negative for H.pylori. After endoscopic examination, additional venous blood samples were taken from the children to determine vitamin D levels. A controlled study was carried out 45days after the initial treatment. The overall success rate of eradication therapy was 84.1 %. In group A, the success rate of treatment was 93.5 %, contrary to group B, where the success rate was 75 %. Although there was a difference in the percentage of H.pylori eradication therapy in the main group compared to the control group, there was no significant difference in group B. The success rate of eradication is p=0.082. Following the research results, the addition of vitamin D to the standard triple therapy regimen for H.pylori had no effect. It can therefore be concluded that vitamin D does not significantly increase the efficacy of eradication therapy.

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