Digitalization of toxicology: improving preclinical to clinical translation.

Though the portfolio of medicines that are extending and improving the lives of patients continues to grow, drug discovery and development remains a challenging business on its best day. Safety liabilities are a significant contributor to development attrition where the costliest liabilities to both drug developers and patients emerge in late development or post-marketing. Animal studies are an important and influential contributor to the current drug discovery and development paradigm intending to provide evidence that a novel drug candidate can be used safely and effectively in human volunteers and patients. However, translational gaps-such as toxicity in patients not predicted by animal studies-have prompted efforts to improve their effectiveness, especially in safety assessment. More holistic monitoring and "digitalization" of animal studies has the potential to enrich study outcomes leading to datasets that are more computationally accessible, translationally relevant, replicable, and technically efficient. Continuous monitoring of animal behavior and physiology enables longitudinal assessment of drug effects, detection of effects during the animal's sleep and wake cycles and the opportunity to detect health or welfare events earlier. Automated measures can also mitigate human biases and reduce subjectivity. Reinventing a conservative, standardized, and traditional paradigm like drug safety assessment requires the collaboration and contributions of a broad and multi-disciplinary stakeholder group. In this perspective, we review the current state of the field and discuss opportunities to improve current approaches by more fully leveraging the power of sensor technologies, artificial intelligence (AI), and animal behavior in a home cage environment.

Dietary inclusion of Withania somnifera and Asparagus racemosus induces growth, activities of digestive enzymes, and transcriptional modulation of MyoD, MyoG, Myf5, and MRF4 genes in fish, Channa punctatus.

The present study explores growth potential of two medicinal herbs, Withania somnifera (Ashwagandha or 'A') and Asparagus racemosus (Shatavari or 'S') after their dietary inclusion in fish, Channa punctatus (13.5 ± 2 g; 11.5 ± 1 cm). Three hundred well-acclimatized fish were distributed into 10 groups- C (Control), S1 (1% S), S2 (2% S), S3 (3% S), A1 (1% A), A2 (2% A), A3 (3% A), AS1 (1% A and S), AS2 (2% A and S), and AS3 (3% A and S), each having 10 specimens. Fish were fed with these diets for 60 days. The study was performed in triplicate. Growth indices- weight gain (WG), specific growth rate percentage (SGR%), feed intake (FI), and condition factor (CF), after 30 and 60 days, were found significantly (p < 0.05) up-regulated in all the groups, except S1, when compared to the C. A significant (p < 0.05) increase in final body weight (FBW) was noticed in all the groups, except S1, after 60 days. Relative to the control group, activities of lipase and amylase in the gut tissue were elevated in all groups, at both sampling times, with the exception of lipase in S1 at 60 days, and amylase in S1 at day 30 and day 60 and S2 at day 60. The mRNA expression of myogenic regulatory factors (MRFs) was also found to be significantly (p < 0.05) up-regulated with the highest fold changes recorded in AS3 for myoD (3.93 ± 0.91); myoG (6.71 ± 0.30); myf5 (4.40 ± 0.33); MRF4 (4.94 ± 0.21) in comparison to the C.

A Review of the Occurrence of Rheumatoid Arthritis and Potential Treatments through Medicinal Plants from an Indian Perspective.

Arthritis is a medical condition that affects the joints and causes inflammation, pain, and stiffness. There are different types of arthritis, and it can affect people of all ages, even infants and the elderly. Recent studies have found that individuals with diabetes, heart disease, and obesity are more likely to experience arthritis symptoms. According to the World Health Organization, over 21% of people worldwide suffer from musculoskeletal problems. Roughly 42.19 million individuals in India, constituting around 0.31% of the populace, have been documented as having Rheumatic Artheritis (RA). Compared to other common diseases like diabetes, cancer, and AIDS, arthritis is more prevalent in the general population. Unfortunately, there is no specific cure for arthritis, and treatment plans usually involve non-pharmacological methods, surgeries, and medications that target specific symptoms. Plant-based remedies have also been shown to be effective in managing inflammation and related complications. In addition to therapies, maintaining a healthy diet, exercise, and weight management are essential for managing arthritis. This review discusses the causes, prevalence, diagnostic methods, current and prospective future treatments, and potential medicinal plants that may act as anti-inflammatory or anti-rheumatic agents. However, more research is necessary to identify the underlying mechanisms and active molecules that could improve arthritis treatment.

Bilateral sixth nerve palsy with subdural hematoma: a unique presentation of B12 deficiency.

Vitamin B12 is inextricably associated with the development and maintenance of neuronal functions. It is classically associated with subacute combined degeneration and peripheral neuropathy; however, cranial neuropathy is uncommon. We observed the rarest neurological manifestation of B12 deficiency. A 12 months infant had history of lethargy, irritability, anorexia, paleness, vomiting, and neurodevelopmental delay for 2 months. He also developed inattention and altered sleep pattern. His mother noticed bilateral inward rotation of both eyes. On examination, the infant had bilateral lateral rectus palsy. The infant was found to have anemia (7.7g/dL) and severe B12 deficiency (74pg/mL). On MRI, there was cerebral atrophy, subdural hematoma (SDH) and wide cisternal spaces and sulci. On supplementation with cobalamin, he improved clinically though mild restriction of lateral gaze on the left side persists. Follow up MRI showed significant improvement in cerebral atrophy with resolution of SDH. To date, such clinical presentation of B12 deficiency has never been reported. The authors suggest B12 supplementation for at risk population esp at antenatal stage and lactating mothers in national programs. The treatment of this condition should be initiated early to prevent long term sequelae.

Homocysteine, Vitamin B12 and Folate Level: Possible Risk Factors in the Progression of Chronic Heart and Kidney Disorders.

Cobalamin is an essential molecule for humans; it is exceptionally important for various body functions, including deoxyribonucleic acid synthesis and cellular energy production. Vegans are more vulnerable to vitamin B12 deficiency than natives with moderate consumption of animal dietary supplements or people with inadequate nutritional patterns. However, the long-term effects of sub-medical deficiency have not been thoroughly studied, but they may have a negative impact on the cardiovascular system, pregnancy outcomes, and vascular, renal, cognitive, bone, and eye health. Alongside the statin remedy, that is a powerful approach for CVD prevention. Another approach is related to the B nutrition substitution remedy with folic acid, and vitamins B6 and B12 are extensively practised nowadays. There is a tremendous interest in plasma homocysteine (tHcy) as a cardiovascular hazard factor. However, current research in the field of its prevention is more inclined toward confirming the benefit of tHcy-reducing remedy with vitamin B12. Thus, while folic acid fortification is primarily aimed at reducing neural-tube defects, it may also play a significant role in the primary prevention of CVD by lowering tHcy. Folate and B-vitamins play important roles in CVD prevention and nutrition policy implementation. Patients affected with Chronic Kidney Disease (CKD) or end-stage Stage Renal Disease (ESRD) experience a tremendous cardiovascular threat that may also further lead to death. As a result, routine monitoring of vitamin B12 levels is likely to be beneficial for the early detection and treatment of metabolic vitamin B12 deficiency, as well as the prevention of heart-related diseases.

Evaluation of immunostimulatory attributes of Asparagus racemosus and Withania somnifera supplemented diets in fish, Channa punctatus (Bloch, 1793).

With the progression of aquaculture industry, there has been a spurt in dietary supplementation with economically viable medicinal herbs having enough immunostimulatory potential. This also aids in avoidance of environmentally undesirable therapeutics that are almost inevitable to safeguard fish against an array of diseases in aquaculture practices. The study aims to determine the optimal dose of herbs that can stimulate substantial immune response in fish for reclamation of aquaculture. Immunostimulatory potential of the two medicinal herbs- Asparagus racemosus (Shatavari), Withania somnifera (Ashwagandha), individually, and in combination, with a basal diet was screened up to 60 days in Channa punctatus. 300 laboratory acclimatized healthy fish (14 ± 1 g; 11 ± 1 cm) were divided into ten groups- C, S1, S2, S3, A1, A2, A3, AS1, AS2, and AS3, based on the composition of dietary supplementation, in triplicates, with 10 specimens per group. The hematological index, total protein and lysozyme enzyme activity were performed after 30 and 60 days, while qRT-PCR analysis of lysozyme expression was done after 60 days of the feeding trial. The significant (P < 0.05) increments in hematological indices- (TEC, TLC, DLC, Hb, Hct, MCV, MCH and MCHC), total protein content and serum lysozyme activity, after 30 and 60 days; whereas upregulation of lysozyme transcript levels, both in liver and muscle tissues after 60 days of the feeding trial were recorded in groups- AS1, AS2, and AS3. The maximal increment in lysozyme expression was recorded in AS3, both in liver and muscle tissues, with 3.75 ± 0.13 and 3.21 ± 0.18-folds, respectively. However, increments were non-significant (P > 0.05) for MCV in AS2 and AS3 after 30 days; and for MCHC in AS1 for both the durations; whereas in AS2 and AS3, after 60 days of the feeding trial. A positive correlation (P < 0.05) among lysozyme expression, MCH, lymphocytes, neutrophils, total protein content, and serum lysozyme activity in AS3, after 60 days, conclusively, evinces that a 3% dietary supplementation with both A. racemosus and W. somnifera enhances immunity and health profile of the fish, C. punctatus. The study, thus finds ample scope in augmentation of aquaculture production and also paves the way for more researches for biological screenings of potential immunostimulatory medicinal herbs that can be appropriately incorporated in the fish diet.

Effect of Vitamin D Supplementation on Serum Hepcidin Levels in Non-Diabetic Chronic Kidney Disease Patients.

Introduction: Vitamin D deficiency and anemia frequently coexist. Moreover, vitamin D deficiency is found to play a role in chronic kidney disease (CKD)-associated anemia. We investigated the effect of cholecalciferol on serum hepcidin levels in vitamin D-deficient, non-diabetic individuals with CKD in a randomized, double-blind, placebo-controlled trial. Methods: This study was performed on stored samples of our previously published randomized, double-blind, placebo-controlled trial of cholecalciferol supplementation in non-diabetic patients with stage III-IV CKD and vitamin D deficiency. Stable patients of either sex, aged 18-70 years, with non-diabetic stage III-IV CKD (estimated glomerular filtration rate between 15 and 60 ml/min/1.73 m2), and having serum 25-hydroxyvitamin D3 [25(OH) D] levels ≤20 ng/ml were included. Participants received either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and at eight weeks. Follow-up was done at 16 weeks. Serum hepcidin levels were analyzed at baseline and at 16 weeks. Results: A total of 120 CKD patients were enrolled. Serum 25(OH) D levels were similar in the placebo and cholecalciferol groups at baseline (13.21 ± 4.78 ng/ml and 13.40 ± 4.42 ng/ml; P = 0.88). After 16 weeks, the serum 25(OH) D levels were found to be increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change 23.40 ng/ml; 95% CI: 19.76 to 27.06; P < 0.001). Serum hepcidin levels were similar at baseline (median [IQR]: 33.6 [8.6-77.8] ng/ml vs. 24.6 [9.3-70.7] ng/ml, P = 0.903) and did not vary between groups at 16 weeks (median [IQR]: 41.5 [10.9-75.0] ng/ml vs. 34.8 [12.3-63.75] ng/ml, P = 0.703). Conclusion: Our study provides preliminary data based on which a larger adequately powered clinical trial can be conducted to conclusively assess the impact of vitamin D supplementation on hepcidin levels and anemia in patients with CKD and vitamin D deficiency.

Cholecalciferol supplementation and angiogenic markers in chronic kidney disease.

Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3-4. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and 13.40±4.42 ng/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to 27.06; p<0.001). Serum levels of angiogenic markers were similar at baseline. At 16 weeks, angiopoietin-2 level decreased in cholecalciferol group (mean difference:-0.73 ng/ml, 95%CI, -1.25 to -0.20, p = 0.002) but not in placebo group (mean difference -0.46 ng/ml, 95%CI, -1.09 to 0.17, p = 0.154), however there was no between-group difference at 16 weeks (between-group difference in mean change: -0.27 ng/ml, 95%CI, -1.09 to 0.55, p = 0.624). Serum angiopoietin-1 level increased [mean change: 5.63 (0.51 to 10.75), p = 0.018] and VEGF-R level decreased [mean change: -87.16 (-131.89 to -42.44), p<0.001] in placebo group but did not show any change in cholecalciferol group. Our data shows the changes in Ang-1, Ang-2 and Ang-1/Ang-2 ratio after high dose oral cholecalciferol supplementation in patients with non-diabetic G3-4 CKD. The data suggests changes in circulating levels of angiogenic markers which needs to be confirmed through an adequately powered study.

Cannabis: Chemistry, extraction and therapeutic applications.

Cannabis, a genus of perennial indigenous plants is well known for its recreational and medicinal activities. Cannabis and its derivatives have potential therapeutic activities to treat epilepsy, anxiety, depression, tumors, cancer, Alzheimer's disease, Parkinson's disease, to name a few. This article reviews some recent literature on the bioactive constituents of Cannabis, commonly known as phytocannabinoids, their interactions with the different cannabinoids and non-cannabinoid receptors as well as the significances of these interactions in treating various diseases and syndromes. The biochemistry of some notable cannabinoids such as tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, cannabichromene and their carboxylic acid derivatives is explained in the context of therapeutic activities. The medicinal features of Cannabis-derived terpenes are elucidated for treating several neuro and non-neuro disorders. Different extraction techniques to recover cannabinoids are systematically discussed. Besides the medicinal activities, the traditional and recreational utilities of Cannabis and its derivatives are presented. A brief note on the legalization of Cannabis-derived products is provided. This review provides comprehensive knowledge about the medicinal properties, recreational usage, extraction techniques, legalization and some prospects of cannabinoids and terpenes extracted from Cannabis.

Evaluation of Individual Quality of Life (QOL) Among Patients with Tracheostomy Using WHO-QOL BREF Questionnaire.

Tracheostomy is one of the most frequently performed surgical procedures worldwide. The placement of tracheostomy in a patient is associated with significant morbidities as apart from the physical impact of the procedure, a profound and persistent effect on psychosocial, financial, environmental and other aspects of global health of the patient becomes inevitable. However, there is a surprising paucity of literature assessing the Quality of Life (QOL) in patients with tracheostomy tube placement. This study was undertaken with the objective to assess the effect of tracheostomy on Quality of Life (QOL) of patients in an urban tertiary health care setup in India. Patients who underwent tracheostomy tube placement irrespective of the indication were included in the study and followed up for a period of up to 3 months to determine the effect of tracheostomy tube placement on the Quality of Life. A questionnaire based on World Health Organisation (WHO) QOL BREF scheme was utilized to evaluate QOL in the immediate post operative period and again appraised after a period of 3 months. The results were statistically analyzed, tabulated and compared using paired t test to evaluate the 'p' value in every domain i.e., physical, social, psychological and environmental, of the WHO QOL-BREF evaluation tool. 63 patients were enrolled in the study after excluding the patients not fulfilling the selection criteria. The majority of patients were male over the age of 50 years (mean age 57 years). There was a noteworthy depreciation in QOL score in patients as WHO-QOL-BREF scores in all the 4 domains were significantly lower after 3 months. The most affected were the Environmental domain (p value 5E-15) whereas the domain of Psychological showed least depreciation of mean QOL score (p value 7.7E-5). Insertion of a tracheostomy tube has a significant impact on the quality of life of the patient and the amount of burden increases with worsening quality of life. A holistic and scientific approach to assess and manage tracheostomy induced morbidity on the patient is necessary. The patients' views of the aspects of life should be used by health policy makers, clinicians, and caregivers as a reliable guide to the most important priorities for treatment and medical interventions. Large prospective multicenter studies may be undertaken for the developement of a standardized and internationally accepted tracheostomy specific quality of life evaluation tool.

Levofloxacin based non-rifampicin anti-tuberculous therapy: An effective alternative in renal transplant recipients in resource limited setting.

INTRODUCTION: Rifampicin is one of the most effective components of anti-tuberculous therapy (ATT). Since rifampicin is a hepatic enzyme (CYP3A4) inducer, in a post-renal transplant recipient, the dose of calcineurin inhibitors needs to be up-regulated and frequently monitored. In resource-limited (low- and lower-middle-income countries) setting this is not always feasible. Therefore, we evaluated a non-rifampicin-based ATT using levofloxacin in kidney transplant recipients. METHODS: We retrospectively studied the medical records of renal transplant recipients diagnosed with tuberculosis in our institute between 2014 and 2017. After a brief discussion with patients regarding the nature and course of ATT, those who opted for a non-rifampicin based therapy due to financial constraints were included in the study and followed for a minimum of 6 months period after the completion of ATT. RESULTS: Out of the 550 renal transplant recipients, 67 (12.2%) developed tuberculosis after a median period of 24 (1-228) months following transplantation, of them, 64 patients opted for non-rifampicin-based ATT. The mean age was 37.6 years. Only 25% were given anti-thymocyte globulin based induction, while the majority (56; 87.5%) of them were on tacrolimus-based triple-drug maintenance therapy. Extrapulmonary tuberculosis was noted in 33% of cases, while 12 (18.7%) had disseminated disease. The median duration of treatment was 12 months and the cure rate of 93.7% (n = 60) was achieved at the end of therapy. CONCLUSION: Levofloxacin based ATT appears to be a safe and effective alternative of rifampicin in kidney transplant recipients who cannot afford heightened tacrolimus dosage.

An unusual complication of quadriparesis after trigger point injection: a case report.

ABSTRACT: Quadriparesis after intramuscular trigger point injections for myofascial pain syndrome has been rarely reported in the literature. A 37-year-old male patient presented with myofascial pain syndrome and was given trigger point injections in trapezius muscles under ultrasound guidance. The patient noticed weakness in all the 4 limbs at approximately 12 hours after the procedure, which gradually progressed to functional quadriplegia at the time of presentation to the emergency department. On examination, he had quadriparesis with no sensory involvement and superficial reflexes were normal. MRI screening of the whole spine was unremarkable, and MRI brain suggested an incidental granuloma, which could not explain his symptoms. Blood tests revealed severe hypokalemia (2.2 mEq/L) and deranged thyroid function tests. Immediate potassium correction with intravenous and oral potassium chloride was initiated, and the patient showed improvement within 6 hours of initiating correction. Stress of the procedure, use of steroids with mineralocorticoid effects such as methylprednisolone, or deranged thyroid function tests may have acted as triggers to precipitate hypokalemic paralysis in the patient. Knowledge of this complication is essential as prompt diagnosis and timely management of hypokalemia can result in complete resolution of the symptoms.

Application of Standardised Yoga Protocols as the Basis of Physiotherapy Recommendation in Treatment of Sleep Apneas: Moving Beyond Pranayamas.

Yoga is an ancient Indian practice of mental and physical exercises (syn: asanas), postures (syn: mudras), movements and breathing techniques which sustain healthy living of the body and the mind. It incorporates various exercises of breathing, oropharyngeal structures and facial expressions, the physiology and effect of which are comparable to international physiotherapy recommendations in treatment of obstructive sleep apnea (OSA) i.e. to preserve upper airway patency by maintaining airway dilator muscle tone. Preliminary results show that yoga can be an effective and constructive alternative to physiotherapy for sleep apnea and snoring patients. To compare the physiotherapy recommendations in snoring patients with various yoga exercises postures. To determine the efficacy of yoga in treatment of sleep apnea. To formulate a standardized yoga protocol for universal usage in sleep apnea. We studied the available literature on physiotherapy recommendations for OSA and yoga asanas involving the nasal, oropharynx and facial structures and perceived a noteworthy similarity in physiological basis of both. A set of these yogasanas were put together and patients presenting with snoring and diagnosed with mild to moderate sleep apnea were presented and encouraged to perform the standardized set of yoga exercises for a period of 3 months. A total of 23 patients were recommended yoga protocols as initial form of treatment in snoring and mild to moderate sleep apnea. Clinical and statistically significant improvement gauzed by recommended score chart was discerned in majority of subjects. The results were comparable to the efficacy of existing physiotherapy regimen published in international literature. The benefits of yoga in sleep disorders go beyond the scope of measured outcomes. Standardizing the protocols for yoga in treatment for snoring and sleep apnea is the need of the hour. Further studies on efficacy of yoga need to be performed to understand its full realm of potential.

Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex.

Binge eating (BE) is a heritable trait associated with eating disorders and involves episodes of rapid, large amounts of food consumption. We previously identified cytoplasmic FMR1-interacting protein 2 (Cyfip2) as a genetic factor underlying compulsive-like BE in mice. CYFIP2 is a homolog of CYFIP1 which is one of four paternally-deleted genes in patients with Type I Prader-Willi Syndrome (PWS), a neurodevelopmental disorder whereby 70% of cases involve paternal 15q11-q13 deletion. PWS symptoms include hyperphagia, obesity (if untreated), cognitive deficits, and obsessive-compulsive behaviors. We tested whether Cyfip1 haploinsufficiency (+/-) would enhance compulsive-like behavior and palatable food (PF) intake in a parental origin- and sex-dependent manner on two Cyfip2 genetic backgrounds, including the BE-prone C57BL/6N (Cyfip2N/N) background and the BE-resistant C57BL/6J (Cyfip2J/J) background. Cyfip1+/- mice showed increased compulsive-like behavior on both backgrounds and increased PF intake on the Cyfip2N/N background. In contrast, maternal Cyfip1 haploinsufficiency on the BE-resistant Cyfip2J/J background induced a robust escalation in PF intake in wild-type Cyfip1J/J males while having no effect in Cyfip1J/- males. Notably, induction of behavioral phenotypes in wild-type males following maternal Fmr1+/- has previously been reported. In the hypothalamus, there was a paternally-enhanced reduction in CYFIP1 protein whereas in the nucleus accumbens, there was a maternally-enhanced reduction in CYFIP1 protein. Nochange in FMR1 protein (FMRP) was observed in Cyfip1+/- mice, regardless of parental origin. To summarize, Cyfip1 haploinsufficiency increased compulsive-like behavior and induced genetic background-dependent, sex-dependent, and parent-of-origin-dependent effects on PF consumption and CYFIP1 expression that could have relevance for neurodevelopmental and neuropsychiatric disorders.

Green preparation of seaweed-based silver nano-liquid for cotton pathogenic fungi management.

Silver nanoparticles (Ag NPs) were synthesised using the crude ethyl acetate extracts of Ulva lactuca and evaluated their bioefficacy against two crop-damaging pathogens. The sets of lattice planes in the XRD spectrum for the Ag NPs were indexed to the 111, 200, 220 and 311 orientations and support the crystalline nature of the Ag NPs. The 3414 and 2968 cm-1 peaks were observed in crude algal thallus extract and they were characteristic of terpenoids. Further, a peak at 1389 cm-1 was observed as fatty acids. The marine macroalgae terpenoids and palmitic acid acted as reducing agent and stabiliser, respectively. The size (3 and 50 nm) and shape (spherical) of Ag NPs were recorded. The energy-dispersive X-ray spectroscopy analysis exemplified the presence of silver in its elemental nature. Moreover, U. lactuca Ag NPs were effective against two cotton phytopathogens namely Fusarium oxysporum f.sp. vasinfectum (FOV) and Xanthomonas campestris pv. malvacearum (XAM). The minimum inhibitory concentration was found to be 80.0 and 43.33 µg ml-1 against FOV and XAM, respectively. Results confirmed the anti-microbial activity of green nanoparticles against select pathogens and suggest their possible usage in developing antifungal agents for controlling destructive pathogens in a cotton agroecosystem.

Ethnomedicinal, phytochemical and pharmacological updates on Hygrophila auriculata (Schum.) Hiene: an overview.

This article explores the most recent evidence-based information on ethnomedicinal, phytochemical and pharmacological understanding of Hygrophila auriculata for the treatment of various diseases and health conditions. Various ethnomedicinal writings suggest the use of the plant or its parts for the treatment of jaundice, oedema, gastrointestinal ailments, diarrhoea, dysentery, urinogenital disorder, gall stones, urinary calculi, kidney stone, leucorrhoea, rheumatism, tuberculosis, anaemia, body pain, constipation, skin disease, and as an aphrodisiac. The plant has been reported to contain flavonoids (apigenin, luteolin, ellagic acid, gallic acid and quercetin), alkaloids (asteracanthine and asteracanthicine), triterpenes (lupeol, lupenone, hentricontane and betulin), sterols (stigmasterol and asterol), minerals, amino acids, fatty acids, aliphatic esters and essential oils. Extracts and bioactive compounds from the plant have been found to possess antimicrobial, anthelmintic, antitermite, nephroprotective, hepatoprotective, central nervous system protective, antitumour, antidiabetic, anticataract, antioxidant, haematopoietic, diuretic, antinociceptive, anti-inflammatory, antipyretic, antimotility, aphrodisiac, neuroprotection, anti-endotoxin and anti-urolithiatic activities. For this paper, we reviewed patents, clinical studies, analytical studies and marketed formulations from the earliest found examples from 1887 to the end of 2017.

Vascular function and cholecalciferol supplementation in CKD: A self-controlled case series.

Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3-4 CKD (J Am Soc Nephrol 28: 3100-3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH)2D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH)2D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0-7.5%, p < 0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function.

Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney disease.

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤ 20 ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140-260 pg/ml and placebo - median;180 pg/ml, IQR; 140-240 pg/ml, p = 0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p = 0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; -31.94 pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p = 0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r = -0.20, p = 0.03) and positively with Δuric acid (r = 0.37, p < 0.001) but not with Δ25(OH) D (r = 0.06, p = 0.54), Δ iPTH (r = - 0.03, p = 0.78) ΔFGF23 (r = - 0.08, p = 0.38) and Δ125 (OH)2 D (r = - 0.04, p = 0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3-4 CKD subjects.

Isolation of Flavonoids and Flavonoid Glycosides from Myrsine africana and Their Inhibitory Activities against Mushroom Tyrosinase.

Bioassay-guided fractionation of the methanol extract of the shoots of Myrsine africana led to the isolation of the new compound myricetin 3-O-(2″,4″-di-O-acetyl)-α-l-rhamnopyranoside (9) and 11 known compounds. The known compounds quercetin 3-O-(3″,4″-di-O-acetyl)-α-l-rhamnopyranoside (8), rutin (10), quercetin 3-O-α-l-rhamnopyranoside (11), and myricetin 3-O-α-l-rhamnopyranoside (12) are reported for the first time from the methanol extract of the shoots of M. africana. Compounds 10 and 12 showed significant inhibition of tyrosinase with 50% inhibition (IC50 values) of the enzyme at 0.13 ± 0.003 and 0.12 ± 0.002 mM, respectively, which was supported by the docking fitness scores obtained through molecular docking analysis. In addition, compounds 1-12 displayed significant antioxidant activity with IC50 values ranging 1.90 to 3.90 µM.