Carbon dioxide sequestration in natural gas hydrates - effect of flue and noble gases.

Clean energy is one of the immediate requirements all over the world to tackle the global energy demands. Natural gas hydrates (NGHs) are one of the proposed alternatives that could be used to extract methane as clean energy and simultaneously sequestrate carbon dioxide. However, the formation of CH4-CO2 mixed hydrates and the first hydrate layer besides the interface reduces the rate of CO2 sequestration and methane extraction in NGHs, and thus, multistep extraction of methane is one of the proposed solutions. We report the atomic level factors that could enhance CO2 sequestration in the newly formed first hydrate layer besides the interface in the presence of flue and noble gases using DFT calculations and molecular dynamics simulations at 250 K and 0.15 kbar. The simulations show the formation of stable dual cages (large-large or small-large) that lead to the formation of a four-caged, Y-shaped cluster (growth synthon) which leads to the formation of a hydrate unit cell in heterogeneous medium. Among the flue and noble gases, only argon forms energetically favorable dual cages with itself and CO2 due to which enhanced CO2 sequestration is observed at different concentrations of Ar and CO2 where the CO2 : Ar (2.5 : 1.5) system shows the best CO2 sequestration in the first layer besides the interface. The results also provide understanding into the previously reported concentration dependent CO2 selectivity in sI hydrates in the presence of third gases (N2 and H2S).

Effect of Imatinib treatment on renal anaemia in chronic myeloid leukemia patients.

PURPOSE: In this study, we investigate renal function and anaemia during imatinib treatment in patients with chronic myeloid leukaemia. METHODS: The patients with chronic myeloid leukaemia with chronic phase who had been treated with only imatinib for 12 months at Rajiv Gandhi Cancer Institute and Research Centre (New Delhi, India) were enrolled and prospectively analysed. The chronic renal impairment parameters, including estimated glomerular filtration rate and haemoglobin levels for anaemia from June 2020 to June 2022, were monitored in newly diagnosed in patients with chronic myeloid leukaemia-chronic phase. The data were analysed by SPSS software version 22. RESULTS: In total 55 patients with chronic myeloid leukaemia chronic phase who had been on imatinib for 12 months were monitored. The mean estimated glomerular filtration rate was significantly decreased (74 ± 14 to 59 ± 12 mL/min/1.73m2, p < 0.001) with a decrease in mean haemoglobin levels after 12 months (10.9 ± 2.01 to 9.0 ± 1.02, p < 0.004). The decreased estimated glomerular filtration rate was negatively correlated with haemoglobin levels after 1 year of imatinib administration (correlation coefficient = 0.892, R2 = 0.7976, p < 0.05). CONCLUSION: We recommended close monitoring of renal function and haemoglobin levels in patients with chronic myeloid leukaemia patients.

The "Ins and Outs" of Prostate Specific Membrane Antigen (PSMA) as Specific Target in Prostate Cancer Therapy.

Prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with metastasis, progression, and androgen independence. Because of its specificity, PSMA is a major target of prostate cancer therapy; however, detectable levels of PSMA are also found in other tissues, especially in salivary glands and kidney, generating bystander damage of these tissues. Antibody target therapy has been used with relative success in reducing tumor growth and prostate specific antigen (PSA) levels. However, since antibodies are highly stable in plasma, they have prolonged time in circulation and accumulate in organs with an affinity for antibodies such as bone marrow. For that reason, a second generation of PSMA targeted therapeutic agents has been developed. Small molecules and minibodies have had promising clinical trial results, but concerns about their specificity had arisen with side effects due to accumulation in salivary glands and kidneys. Herein we study the specificity of small molecules and minibodies that are currently being clinically tested. We observed a high affinity of these molecules for PSMA in prostate, kidney and salivary gland, suggesting that their effect is not prostate specific. The search for specific prostate target agents must continue so as to optimally treat patients with prostate cancer, while minimizing deleterious effects in other PSMA expressing tissues.

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies.

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

Evaluation of Sida cordifolia and Sida rhombifolia extracts in a rat model of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Sida cordifolia and Sida rhombifolia are regarded as useful herbs as they have been shown to be effective, inexpensive and harmless in the prevention of diabetes, and are recognized as valuable therapeutic substances. OBJECTIVES: The purpose of this study was to assess the effect of S. cordifolia and S. rhombifolia in the treatment of diabetic nephropathy using a rat model. MATERIAL AND METHODS: Extracts of S. cordifolia and S. rhombifolia were obtained using the Soxhlet method. The hydroalcoholic extract solvent was used in the following proportions: 70:30, 50:50 and 80:20. The 80:20 hydroalcoholic extract was observed to be the most potent. The inhibitory effects of the extract were determined using the α-amylase assay. The most potent extract also underwent total flavonoid, phenolic and free radical scavenging tests, and was incorporated into an animal study. Diabetes was induced in rats by administering nicotinamide (NAD; 230 mg/kg) and streptozotocin (STZ; 65 mg/kg) intraperitoneally. In addition to a standard control of pioglitazone, the rats received extract dosages of 100 mg/kg/day or 200 mg/kg/day. Body weight, blood glucose, glycated hemoglobin (HbA1c), blood urea nitrogen (BUN), serum albumin, serum creatinine, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance were assessed at various time points. The animals also underwent histopathological examination to observe alterations induced by the treatment. RESULTS: Sida cordifolia was the most successful in lowering blood glucose and HbA1c levels. Renal function indices and antioxidant enzyme levels were regained in a dose-dependent manner. Furthermore, S. cordifolia (200 mg/kg/day) extract, similar to pioglitazone, inhibited the production of advanced glycation byproducts by the kidney. CONCLUSIONS: The effects of various S. cordifolia and S. rhombifolia extracts on rats with diabetic nephropathy were observed. Sida cordifolia may be further explored for the treatment of diabetic nephropathy and, due to its diverse nature, may be utilized for the treatment of a wide range of diseases, as it provided more significant findings.

Impact of imatinib treatment on renal function in chronic myeloid leukaemia patients.

BACKGROUND: Recently, multiple epidemiological studies have linked imatinib with the alteration of renal function in chronic myeloid leukaemia (CML) patients. This meta-analysis aimed to summarize the impact of imatinib use on renal function in CML patients. METHODS: A systematic search was conducted on MEDLINE and Embase to identify articles assessing the impact of imatinib exposure on renal function in CML patients. The risk of bias was assessed using the Newcastle-Ottawa scale (NOS). Two authors independently performed literature-screening, risk of bias and data extraction. The risk of renal dysfunction (chronic kidney disease or acute kidney injury) among imatinib users was computed as the primary outcome of interest. The certainty of findings was assessed using the grading of recommendations assessment, development and evaluation (GRADE) criteria. RESULTS: A total of nine articles qualified for inclusion in the systematic review, of which four articles were eligible for meta-analysis. Based on the scoring on NOS, majority of the included studies were found to be of moderate risk of bias. Majority of the studies (n = 6) reported significantly (p < .05) decrease in estimated glomerular filtration rate (eGFR) after imatinib treatment. The risk of developing renal dysfunction (chronic kidney disease or acute kidney injury) was found to be significantly higher in imatinib users as compared to other tyrosine kinase inhibitor (TKI) users with a pooled relative risk of 2.70 (95% CI: 1.49-4.91). Sensitivity analysis also revealed a consistently high risk of renal dysfunction with imatinib use. GRADE criteria revealed low certainty of evidence. CONCLUSION: This meta-analysis found an increased risk of renal dysfunction in imatinib users compared to other TKI users.

Microbial consortia adaptation to substrate changes in anaerobic digestion.

Renewable natural gas (RNG) produced from anaerobic digestion (AD) of agricultural residues is emerging a serious biofuel alternative. Complex nature of lignocellulosic biomass residues coupled with complex biochemical transformations involving a large spectrum of microbial communities make anaerobic digestion of biomass difficult to understand and control. The present work aims at studying adaptation of microbial consortia in AD to substrates changes and correlating these to biogas generation. The double edged study deals with (a) using a common starting culture inoculum on different fractions of pretreated lignocellulosic biomass (LBM) fractions; and (b) using different starter inocula for gas generation from simple glucose substrate. Taxonomic analysis using 16S amplicon sequencing is shown to highlight changes in microbial community structure and predominance, majorly in hydrolytic bacterial populations. Observed variations in the rate of digestion with different starter inocula could be related to differences in microbial community structure and relative abundance. Results with different treated biomass fractions as substrates indicated that AD performance could be related to abundance of substrate-specific microbial communities. The work is a step to a deeper understanding of AD processes that may lead to better control and operation of AD for super-scale production of RNG from biomass feedstocks.

Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis.

In the murine testis, self-renewal of spermatogonial stem cells (SSCs) requires glial cell line-derived neurotrophic factor (GDNF) secreted from neighboring somatic cells. However, it not clear how GDNF promotes self-renewal in vivo or what downstream signaling pathways are required for SSC maintenance. We found that GDNF is normally expressed cyclically during spermatogenesis. Stage-specific ectopic expression of GDNF caused the accumulation of a GFRA1+ LIN28- Asingle population, which has enhanced SSC activity compared with wild type, suggesting that GDNF normally limits self-renewal to specific stages. Despite the increase in SSC cell number, EdU labeling during steady-stage spermatogenesis, and during recovery after busulfan-mediated spermatogonial depletion, indicated that GDNF promotes self-renewal by blocking differentiation and not by promoting proliferation. Increased GDNF signaling led to increased phosphorylation of AKT3 in undifferentiated spermatogonia, but not of AKT1 or AKT2, and was independent of RPS6 phosphorylation, suggesting that AKT3 functions in SSC self-renewal or progenitor cell expansion.

Packing polymorphism, odd-even alternation and thermotropic phase transitions in N-,O-diacylethanolamines with varying N-acyl chains. A combined experimental and computational study.

N-,O-Diacylethanolamines (DAEs) are derived by simple esterification of bioactive N-acylethanolamines, which are present in plant and animal tissues. In this study, two homologous series of DAEs, namely N-acyl (n = 8-15), O-palmitoylethanolamines (Nn-O16s) and N-acyl (n = 8-14), O-pentadecanoylethanolamines (Nn-O15s) were synthesized and characterized with respect to thermotropic phase transitions, crystal structures and intermolecular interactions. In addition, computational studies were performed to get a molecular level insight into the role of different factors in selective polymorphism in Nn-O16s and Nn-O15s. Differential scanning calorimetric studies revealed that dry Nn-O16s exhibit odd-even alternation in their calorimetric properties, which is absent in Nn-O15s. The 3-dimensional structures of three Nn-O16s (n = 12-14) and two Nn-O15s (n = 12, 14) have been determined by single-crystal X-ray diffraction. Analysis of the molecular packing in these crystals showed the presence of two packing polymorphs (α and ß) in the crystal lattice of Nn-O16s, whereas only the ß polymorph was observed in the Nn-O15s. Further, intermolecular hydrogen bonding interactions (N-H⋯O and C-H⋯O) and dispersion interactions among acyl chains have been found to stabilize the molecular packing observed in the crystal lattice. Molecular dynamics simulations show that the ß polymorph is slightly energetically preferred over the α polymorph in all the systems due to favorable packing of terminal methyl groups at the interlayers. These findings are relevant for understanding the interactions of the DAEs with membrane lipids and proteins.

A systematic review and meta-analysis of non-adherence to anti-diabetic medication: Evidence from low- and middle-income countries.

BACKGROUND: Non-adherence to anti-diabetic medication is an important cause of uncontrolled blood glucose that leads to complications of diabetes. However, there is a lack of evidence on the burden of and factors associated with non-adherence to anti-diabetic medication among individuals living with diabetes in low-and middle-income countries (LMICs). OBJECTIVES: This systematic literature review and meta-analytic synthesis aims to estimate non-adherence to anti-diabetic medication reported among individuals in LMICs and explores factors affecting non-adherence. METHODS: We systematically searched MEDLINE and Embase to identify studies investigating non-adherence to anti-diabetic medications published from January 2000 to May 2020. Two authors carried out study selection, screening, and data extraction independently. Cross-sectional studies that had been conducted among individuals with diabetes in LMICs were eligible for the selection process. Critical appraisal of the included studies was carried out using the Newcastle Ottawa Scale. Meta-analysis was carried out using Stata 14.2. Random effects model was used to compute the pooled proportion at a 95% confidence interval (CI). RESULTS: Forty-three studies met the inclusion criteria, of which 13 studies were used in meta-analysis. The pooled proportion of non-adherence to anti-diabetic medications using the eight-item Morisky Medication Adherence Scale (MMAS-8) was 43.4% (95% CI: 17.5-69.4; P < 0.001) and 29.1% (95% CI: 19.8-38.4; P < 0.001) when using the cut-off at 80 or 90%. The pooled proportion of non-adherence was 29.5% (95% CI: 25.5-33.5; P = .098) when using the four-item Morisky Medication Adherence Scale (MMAS-4). Using the World Health Organization (WHO) five dimensions of medication adherence framework, the factors contributing to non-adherence were varied, including disease factors, therapy-related factors, healthcare system factor, patient-centred factors, and socio-economic factors. CONCLUSIONS: Non-adherence to anti-diabetic medication remains an ongoing challenge in LMICs and several factors operating at different levels were cited as reasons. Comprehensive intervention strategies are urgently needed to address these factors in effectively tackling medication non-adherence in LMICs.

Impact of metformin therapy on health-related quality of life outcomes in tuberculosis patients with diabetes mellitus in India: A prospective study.

OBJECTIVE: To assess the impact of metformin use on health-related quality of life (HRQoL) in tuberculosis (TB) patients who are presented with type 2 diabetes mellitus (T2DM). METHODOLOGY: In this community-based prospective study, TB patients attending Hakeem Abdul Hameed Centenary Hospital, New Delhi (India) and had comorbidity of T2DM between April 2018 and July 2019 were enrolled. Patients were divided into metformin users and metformin non-users on the basis of the presence of metformin in their routine as antidiabetic drug(s). HRQoL was determined using a validated TB-specific tool (Dhingra and Rajpal-12 scale ie, DR-12) consists of symptom and socio-psychological and exercise adaptation domains. The HRQoL scores were compared at pretreatment (1st visit), end of intensive phase (2nd visit) and end of treatment (3rd visit) between the two groups. RESULTS: A total of 120 patients were enrolled, of which 24 were excluded as they did not respond at follow-up visits. Among the metformin users (n = 48) the mean age of patients was 47.56 years and 62.50% was males. Among the metformin non-users (n = 48), the mean age of patients was 49.02 years and 54.10% was males. The baseline characteristics were similar in both groups except for the substance used history (P = .025), literacy level (P = .048) and BMI (P = .028). Metformin users demonstrated significant improvement in symptom scores (2nd visit: P < .001; 3rd visit: P = .001) and socio-psychological and exercise adaptation scores (2nd visit: P < .0001; 3rd visit: P < .0001) as compared with metformin non-users at 2nd visit and 3rd visit. Overall, scores were also found to be significantly improved in metformin users (2nd visit: P < .001; 3rd visit: P = .001). CONCLUSION: Metformin therapy exerted favourable effects on HRQoL in patients with TB and T2DM and can be recommended as an adjuvant antitubercular drug in TB patients with co-morbidity of T2DM, unless contraindicated.

Understanding fast diffusion of solutes in solid solutions: A molecular dynamics study of solutes in body centered cubic solid.

In some binary alloys, the solute exhibits high or fast diffusion with low activation energy. In order to understand this, diffusion of solute atoms through a lattice of body centered cubic solvent atoms has been investigated with molecular dynamics technique. Surprisingly, solutes exhibit two distinct diffusivity maxima. Solutes migrate through the lattice mainly by diffusion from one tetrahedral void to another (tt) and, less frequently, by diffusion from a tetrahedral to an octahedral void (to) or reverse jumps (ot). Solutes with maximum diffusivity show smooth decay of the velocity autocorrelation function without backscattering. The average force on the solutes of various diameters correlates well with the position and intensity of the diffusivity maxima exhibited by the solutes. This suggests that the explanation for the diffusivity maxima lies in the levitation effect, which suggests a lowered force on the solute at the diffusivity maxima. The activation energy computed for the solutes of different sizes confirms this interpretation as it is lower for the solutes at the diffusivity maxima. Calculations with blocking of octahedral voids show that the second diffusivity maximum has significant contributions from the to diffusion path. These findings obtained here explain the fast solute/impurity atom diffusivity and low activation energies seen in the literature in many of the alloys, such as Co in γ-U and ß-Zr, Cu in Pr, or Au in Th.

Agrobacterium tumefaciens-mediated in planta transformation strategy for development of transgenics in cotton (Gossypium hirsutum L.) with GFP as a visual marker.

Cotton (Gossypium hirsutum L.), a mercantile crop plant, is grown worldwide for fiber and seed oil. As with other economically important crops, cotton is bogged down with many biotic and abiotic stress factors. Towards this, genetic engineering offers numerous protocols to engineer plants for better resilience. However, recalcitrance of cotton to plant tissue culture has been the major constraint for successful in vitro regeneration. Hence, alternate methods that evade tissue culture regeneration have been envisaged. Non tissue culture-based in planta transformation strategies are in vogue due to amenability and ease in the generation of transgenic plants. In the present study, we demonstrate the utility of an in planta transformation protocol and establishment of a stringent selection agent-based screening for the identification of transgenics. The genotype independent nature of the protocol was validated in cotton cv. Pusa 8-6 using GFP. Preliminary transformation efficiency of 28% was achieved with a screening efficiency of 20% in the presence of hygromycin. The proof of T-DNA integration by various molecular and expression analysis in T1 and T2 generations proved that this technique can be employed to generate transgenic cotton.

Determination of isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National tuberculosis Control Program (RNTCP) in India.

Isoniazid is the most commonly used drug for treatment of tuberculosis, and is administered individually or in combination with other drugs as standard first line therapy. Offsetting its efficacy, severe adverse effects, especially peripheral neuropathy and hepatotoxicity, are associated with isoniazid therapy, limiting its use in tuberculosis. Isoniazid is acetylated in vivo producing hydrazine and acetyl hydrazine, which are responsible for hepatotoxicity. Marked pharmacogenetic differences in acetylation have been reported among different population across the globe. This study evaluates isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National Tuberculosis Control Program (RNTCP) in a specialized tuberculosis hospital in north India. Of 351 patients from whom samples were taken for biochemical analysis of adverse events, 36 were assessed for acetylation patterns. Blood samples were taken 1 h after administration of a 600 mg dose of isoniazid, and plasma concentrations of isoniazid were determined using a validated HPLC method. Of these 36 patients, 20 (55.56%) were slow acetylators and 16 (44.44%) were fast acetylators. Our results are consistent with those of an earlier study conducted in a different region of India. Most biochemical changes produced during long-term isoniazid therapy resolve after therapy is terminated.

Adverse drug reaction prevalence and mechanisms of action of first-line anti-tubercular drugs.

PURPOSE: Understanding the appearance of anti-tubercular drug-related adverse drug reactions (ADRs) in patients receiving tuberculosis (TB) treatment is important, and may be related to morbidity and mortality if not recognized early. Here, we aimed to characterize the mechanisms underlying adverse drug reactions due to combination anti-tuberculosis therapy of the Revised National Tuberculosis Control Program (RNTCP). METHODS: This was a prospective observational study conducted in 9 DOTS centers of New Delhi, India. All enrolled TB patients receiving first-line tuberculosis treatment as per RNTCP guidelines were monitored for ADRs. All ADRs that appeared during the treatment were recorded and analyzed. RESULTS: The study included 1011 TB patients on anti-TB treatment under DOTS. According to Naranjo's probability scale, of a total 351 (34.72%) reported adverse events, 102 (10.09%) were definite, 59 (5.83%) probable, 123 (12.17%) possible, and 67 (6.63%) doubtful. On the Hartwig severity scale, of the 351 adverse drug events, 225 (22.26%) were mild, 105 (10.38%) were moderate, and 21 (2.08%) were severe. Out of 102 reported adverse drug reactions, 81 (79.41%) were moderate and 21 (20.59%), while 65.28% did not experience any ADRs. CONCLUSIONS: Directly Observed Treatment (DOT) is effective and safe compared to daily treatment regimens. Patients receiving DOTS therapy needed close monitoring for adverse events. Therefore, a pharmacovigilance program should be added at the National level to accesses the adverse event incidence.

Sex differences in antihypertensive drug use and blood pressure control.

BACKGROUND: Hypertension is the most important modifiable cardiovascular risk factor. Epidemiological studies have shown the benefits of lowering blood pressure (BP), but BP control is a major challenge. Furthermore, there are significant sex differences in antihypertensive drug use and BP control. This study examined sex differences in antihypertensive drug use and BP control, with the aim of reducing the complications of hypertension and improving quality of life. METHODS: The study was performed in our outpatient hypertension clinic, and included 1529 patients without secondary hypertension or comorbidities. The study, investigated BP control rates and patterns of antihypertensive drug use in male and female. All data were collected using structured questionnaires and patient measurements. RESULTS: The study included 713 males and 816 females in this study. Fewer females had hypertension in the younger age group (16.2% vs 11.6%; p>0.05), but this difference disappeared in middle-aged (47.8% vs 49.9 %; p<0.05) and elderly age groups (36.0% vs 38.5%; p<0.05). BP control rates differed between males and females (35.6% in male, 31.9% in female, p<0.01). There was an overall difference in BP control rates between males and females (35.6% in males, 31.9% in females, p<0.01). In this aged 18-44 years, angiotensin converting enzyme inhibitors (ACEIs) showed the best control rate in males, while calcium channel blockers (CCBs) were least effective (61.5% with ACEIs, 28.6% with CCBs; p<0.05). In this aged 45-64 years, diuretics (DUs) showed the best control rate in females, while CCBs were least effective (47.5% with DUs, 28.3% with CCBs; p<0.05). CONCLUSIONS: Sex plays an important role in BP control. In those aged 18-44 years, males using ACEIs showed best control rates. In those aged 45-64 years, females using DUs showed best control rates. Our study provides a basis with the selection of antihypertensive drugs according to sex and age.

Compound Heterozygosity for Y Box Proteins Causes Sterility Due to Loss of Translational Repression.

The Y-box proteins YBX2 and YBX3 bind RNA and DNA and are required for metazoan development and fertility. However, possible functional redundancy between YBX2 and YBX3 has prevented elucidation of their molecular function as RNA masking proteins and identification of their target RNAs. To investigate possible functional redundancy between YBX2 and YBX3, we attempted to construct Ybx2-/-;Ybx3-/- double mutants using a previously reported Ybx2-/- model and a newly generated global Ybx3-/- model. Loss of YBX3 resulted in reduced male fertility and defects in spermatid differentiation. However, homozygous double mutants could not be generated as haploinsufficiency of both Ybx2 and Ybx3 caused sterility characterized by extensive defects in spermatid differentiation. RNA sequence analysis of mRNP and polysome occupancy in single and compound Ybx2/3 heterozygotes revealed loss of translational repression almost exclusively in the compound Ybx2/3 heterozygotes. RNAseq analysis also demonstrated that Y-box protein dose-dependent loss of translational regulation was inversely correlated with the presence of a Y box recognition target sequence, suggesting that Y box proteins bind RNA hierarchically to modulate translation in a range of targets.

Diabetes prevalence and its impact on health-related quality of life in tuberculosis patients.

OBJECTIVE: To determine the prevalence of diabetes mellitus (DM), assess its influence on health-related quality of life (HRQoL) among patients with TB. METHODS: In this prospective study, eligible patients at three primary healthcare centres in urban slum region of south Delhi, India, underwent blood glucose screening at treatment initiation. HRQoL scores were determined by conducting face-to-face interviews using Dhingra and Rajpal (DR-12) scale at pre-treatment, end of intensive phase and end of the treatment. RESULTS: In 316 patients, the overall DM prevalence was 15.8%, of whom 9.5% were known to have diabetes, and 6.3% were diagnosed at TB treatment initiation. DM was more common among patients of older age (P < 0.001), with higher BMI (P < 0.001), with PTB (P = 0.02) and with poor psychological status. HRQoL was significantly poor in the socio-psychological & exercise adaptation domain in patients with DM ˃50 years of age at each visit. Older age, poor literacy, loss in workdays, alcohol use and socio-economic status significantly predict poor HRQoL scores in patients with DM. Uncontrolled DM patients demonstrated poor HRQoL at the end of the intensive phase (P = 0.04) of treatment and at its completion (P = 0.03) compared to those with controlled DM. CONCLUSION: Addressing screening measures and glycaemic control along with social determinants such as literacy level and alcohol consumption could be an important means of improving the HRQoL of TB with DM patients.

Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats.

BACKGROUND: The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analogue in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and inflammation. In this project we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. METHODS: The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20 mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats - keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa. RESULTS: P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and 69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed good protective effect against ethanol-acid induced gastric mucosal injury in the rats. Administration of the extract's doses (100, 200 and 400 mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of mucosal layer and significantly prevented the formation of hemorrhage and edema. CONCLUSIONS: The investigation suggests that methanolic extract of P. niruri leaf possess anti-inflammatory activity and promotes ulcer protection as ascertained by regeneration of mucosal layer and substantial prevention of the formation of hemorrhage and edema.

2-Benzamido-4-methylthiazole-5-carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers.

The new chemical entities febuxostat and topiroxostat have been approved by the US Food and Drug Administration, opening new avenues for exploiting different heterocycles other than purines as xanthine oxidase (XO) inhibitors. A different series of substituted 2-benzamido-4-methylthiazole-5-carboxylic acid derivatives (5a-r) was synthesized and characterized by the collective use of IR, 1 H and 13 C NMR, and mass spectroscopy, for the treatment of gout and hyperuricemia. In vitro studies of the synthesized derivatives revealed that the presence of a fluoro group at the para position in 5b (IC50 = 0.57 µm) and a chloro group in 5c (IC50 = 0.91 µm) signifies excellent XO inhibitory activity among the series, along with their DPPH free radial scavenging activity. In vivo serum uric acid inhibition studies established that 5b and 5c displayed 62 and 53% uric acid inhibition, respectively. Studies on enzyme kinetics indicated that 5b acts as a mixed type inhibitor. In silico prediction by various softwares also helped in the recognition of potent XO inhibitors.