ABL1 kinase plays an important role in spontaneous and chemotherapy-induced genomic instability in multiple myeloma.

ABSTRACT: Genomic instability contributes to cancer progression and is at least partly due to dysregulated homologous recombination (HR). Here, we show that an elevated level of ABL1 kinase overactivates the HR pathway and causes genomic instability in multiple myeloma (MM) cells. Inhibiting ABL1 with either short hairpin RNA or a pharmacological inhibitor (nilotinib) inhibits HR activity, reduces genomic instability, and slows MM cell growth. Moreover, inhibiting ABL1 reduces the HR activity and genomic instability caused by melphalan, a chemotherapeutic agent used in MM treatment, and increases melphalan's efficacy and cytotoxicity in vivo in a subcutaneous tumor model. In these tumors, nilotinib inhibits endogenous as well as melphalan-induced HR activity. These data demonstrate that inhibiting ABL1 using the clinically approved drug nilotinib reduces MM cell growth, reduces genomic instability in live cell fraction, increases the cytotoxicity of melphalan (and similar chemotherapeutic agents), and can potentially prevent or delay progression in patients with MM.

Elevated APE1 Dysregulates Homologous Recombination and Cell Cycle Driving Genomic Evolution, Tumorigenesis, and Chemoresistance in Esophageal Adenocarcinoma.

BACKGROUND & AIMS: The purpose of this study was to identify drivers of genomic evolution in esophageal adenocarcinoma (EAC) and other solid tumors. METHODS: An integrated genomics strategy was used to identify deoxyribonucleases correlating with genomic instability (as assessed from total copy number events in each patient) in 6 cancers. Apurinic/apyrimidinic nuclease 1 (APE1), identified as the top gene in functional screens, was either suppressed in cancer cell lines or overexpressed in normal esophageal cells and the impact on genome stability and growth was monitored in vitro and in vivo. The impact on DNA and chromosomal instability was monitored using multiple approaches, including investigation of micronuclei, acquisition of single nucleotide polymorphisms, whole genome sequencing, and/or multicolor fluorescence in situ hybridization. RESULTS: Expression of 4 deoxyribonucleases correlated with genomic instability in 6 human cancers. Functional screens of these genes identified APE1 as the top candidate for further evaluation. APE1 suppression in EAC, breast, lung, and prostate cancer cell lines caused cell cycle arrest; impaired growth and increased cytotoxicity of cisplatin in all cell lines and types and in a mouse model of EAC; and inhibition of homologous recombination and spontaneous and chemotherapy-induced genomic instability. APE1 overexpression in normal cells caused a massive chromosomal instability, leading to their oncogenic transformation. Evaluation of these cells by means of whole genome sequencing demonstrated the acquisition of changes throughout the genome and identified homologous recombination as the top mutational process. CONCLUSIONS: Elevated APE1 dysregulates homologous recombination and cell cycle, contributing to genomic instability, tumorigenesis, and chemoresistance, and its inhibitors have the potential to target these processes in EAC and possibly other cancers.

Partial Thermal Condensation Mediated Synthesis of High-Density Nickel Single Atom Sites on Carbon Nitride for Selective Photooxidation of Methane into Methanol.

Direct selective transformation of greenhouse methane (CH4) to liquid oxygenates (methanol) can substitute energy-intensive two-step (reforming/Fischer-Tropsch) synthesis while creating environmental benefits. The development of inexpensive, selective, and robust catalysts that enable room temperature conversion will decide the future of this technology. Single-atom catalysts (SACs) with isolated active centers embedded in support have displayed significant promises in catalysis to drive challenging reactions. Herein, high-density Ni single atoms are developed and stabilized on carbon nitride (NiCN) via thermal condensation of preorganized Ni-coordinated melem units. The physicochemical characterization of NiCN with various analytical techniques including HAADF-STEM and X-ray absorption fine structure (XAFS) validate the successful formation of Ni single atoms coordinated to the heptazine-constituted CN network. The presence of uniform catalytic sites improved visible absorption and carrier separation in densely populated NiCN SAC resulting in 100% selective photoconversion of (CH4) to methanol using H2O2 as an oxidant. The superior catalytic activity can be attributed to the generation of high oxidation (NiIII═O) sites and selective C─H bond cleavage to generate •CH3 radicals on Ni centers, which can combine with •OH radicals to generate CH3OH.

Identification of genetic variants affecting reproduction traits in Vrindavani cattle.

Genome-wide association studies (GWAS) are one of the best ways to look into the connection between single-nucleotide polymorphisms (SNPs) and the phenotypic performance. This study aimed to identify the genetic variants that significantly affect the important reproduction traits in Vrindavani cattle using genome-wide SNP chip array data. In this study, 96 randomly chosen Vrindavani cows were genotyped using the Illumina Bovine50K BeadChip platform. A linear regression model of the genome-wide association study was fitted in the PLINK program between genome-wide SNP markers and reproduction traits, including age at first calving (AFC), inter-calving period (ICP), dry days (DD), and service period (SP) across the first three lactations. Information on different QTLs and genes, overlapping or adjacent to genomic coordinates of significant SNPs, was also mined from relevant databases in order to identify the biological pathways associated with reproductive traits in bovine. The Bonferroni correction resulted in total 39 SNP markers present on different chromosomes being identified that significantly affected the variation in AFC (6 SNPs), ICP (7 SNPs), DD (9 SNPs), and SP (17 SNPs). Novel potential candidate genes associated with reproductive traits that were identified using the GWAS methodology included UMPS, ITGB5, ADAM2, UPK1B, TEX55, bta-mir-708, TMPO, TDRD5, MAPRE2, PTER, AP3B1, DPP8, PLAT, TXN2, NDUFAF1, TGFA, DTNA, RSU1, KCNQ1, ADAM32, and CHST8. The significant SNPs and genes associated with the reproductive traits and the enriched genes may be exploited as candidate biomarkers in animal improvement programs, especially for improved reproduction performance in bovines.

Nanoapatite-Loaded κ-Carrageenan/Poly(vinyl alcohol)-Based Injectable Cryogel for Hemostasis and Wound Healing.

Immediate control of excessive bleeding and prevention of infections are of utmost importance in the management of wounds. Cryogels have emerged as promising materials for the rapid release of medication and achieving hemostasis. However, their quick release properties pose the challenge of exposing patients to high concentrations of drugs. In this study, hybrid nanocomposites were developed to address this issue by combining poly(vinyl alcohol) and κ-carrageenan with whitlockite nanoapatite (WNA) particles and ciprofloxacin, aiming to achieve rapid hemostasis and sustained antibacterial effects. A physically cross-linked cryogel was obtained by subjecting a blend of poly(vinyl alcohol) and κ-carrageenan to successive freezing-thawing cycles, followed by the addition of WNA. Furthermore, ciprofloxacin was introduced into the cryogel matrix for subsequent evaluation of its wound healing properties. The resulting gel system exhibited a 3D microporous structure and demonstrated excellent swelling, low cytotoxicity, and outstanding mechanical properties. These characteristics were evaluated through analytical and rheological experiments. The nanocomposite cryogel with 4% whitlockite showed extended drug release of 71.21 ± 3.5% over 21 days and antibacterial activity with a considerable growth inhibition zone (4.19 ± 3.55 cm). Experiments on a rat model demonstrated a rapid hemostasis property of cryogels within an average of 83 ± 4 s and accelerated the process of wound healing with 96.34% contraction compared to the standard, which exhibited only ∼78% after 14 days. The histopathological analysis revealed that the process of epidermal re-epithelialization took around 14 days following the skin incision. The cryogel loaded with WNAs and ciprofloxacin holds great potential for strategic utilization in wound management applications as an effective material for hemostasis and anti-infection purposes.

Benefits of Rib Fixation Utilizing Low-Cost Materials: A Randomized Pilot Trial.

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) using standard rib plating systems has become a norm in developed countries. However, the procedure has not garnered much interest in low-middle-income countries, primarily because of the cost. METHODS: This was a single-center pilot randomized trial. Patients with severe rib fractures were randomized into two groups: SSRF and nonoperative management. SSRF arm patients underwent surgical fixation in addition to the tenets of nonoperative management. Low-cost materials like stainless steel wires and braided polyester sutures were used for fracture fixation. The primary outcome was to assess the duration of hospital stay. RESULTS: Twenty-two patients were randomized, 11 in each arm. Per-protocol analysis showed that the SSRF arm had significantly reduced duration of hospital stay (22.6 ± 19.1 d versus 7.9 ± 5.7 d, P value 0.031), serial pain scores at 48 h and 5 d (median score 5, IQR (3-6) versus median score 7, IQR (6.5-8), P value 0.004 at 48 h and median score 2 IQR (2-3) versus median score 7 IQR (4.5-7) P value 0.0005 at 5 d), significantly reduced need for injectable opioids (9.9 ± 3.8 mg versus 4.4 ± 3.4 mg, P value 0.003) and significantly more ventilator-free days (19.9 ± 8.7 d versus 26.4 ± 3.2 d, P value 0.04). There were no statistically significant differences in the total duration of ICU stay (median number of days 2, IQR 1-4.5 versus median number of days 7, IQR 1-14, P value 0.958), need for tracheostomy (36.4% versus 0%, P value 0.155), and pulmonary and pleural complications. CONCLUSIONS: SSRF with low-cost materials may provide benefits similar to standard rib plating systems and can be used safely in resource-poor settings.

Protective effect of rutin on acrylamide induced ovarian inflammation, oxidative stress, DNA damage, and hormonal changes: Based on in silico and in vivo study.

Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.

Surgical Cholecystectomy Score (SCS) for grading the difficulty of laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard of care for symptomatic gall stone disease. A good scoring system is necessary to standardize the reporting. Our aim was to develop and validate an objective scoring system, the Surgical Cholecystectomy Score (SCS) to grade the difficulty of LC. METHODS: The study was conducted in a single surgical unit at a tertiary care hospital in two phases from January 2017 to April 2021. Retrospective data was analysed and the difficulty of each procedure was graded according to the modified Nassar's scoring system. Significant preoperative and intraoperative data obtained was given a weightage score. In phase II, these scores were validated on a prospective cohort. Each procedure was classified either as easy, moderately difficult or difficult. STATISTICAL ANALYSIS: A univariate analysis was performed on the data followed by a multivariate regression analysis. Bidirectional stepwise selection was done to select the most significant variables. The Beta /Schneeweiss scoring system was used to generate a rounded risk score. RESULTS: Data of 800 patients was retrieved and graded. 10 intraoperative parameters were found to be significant. Each variable was assigned a rounded risk score. The final SCS range for intraoperative parameters was 0-15. The scoring system was validated on a cohort of 249 LC. In the final scoring, cut off SCS of > 8 was found to correlate with difficult procedures. Score of < 2 was equivalent to easy LC. A score between 2 and 8 indicated moderate difficulty. The area under ROC curve was 0.98 and 0.92 for the intraoperative score indicating that the score was an excellent measure of the difficulty level of LCs. CONCLUSION: The scoring system developed in this study has shown an excellent correlation with the difficulty of LC. It needs to be validated in different cohorts and across multiple centers further.

Neck Circumference in Polycystic Ovary Syndrome: A Systematic Review and Bootstrapped Meta-Analysis with GRADE Approach.

INTRODUCTION: Our aim was to perform a systematic review and meta-analysis for the association of neck circumference (NC) in polycystic ovary syndrome (PCOS) patients as compared to non-PCOS controls. METHODS: Primarily the PubMed/MEDLINE database and others such as SCOPUS, Google Scholar, Cochrane Library, were searched up to November 15, 2023 for observational studies comparing NC in PCOS versus non-PCOS women. The mean and SD values of NC and other covariates in PCOS and control groups were extracted by two independent reviewers, and the quality and risk of bias assessment was done using Newcastle-Ottawa Scale. The meta-analysis employed combined standardized mean differences (SMD) with 95% confidence intervals (CI) to compare NC between PCOS patients and controls. The heterogeneity and validity were addressed by subgroup, meta-regression, and sensitivity analyses. We conducted a Bootstrapped meta-analysis using 1,000 and 10,000 simulations to test the accuracy of the obtained results. The certainty of evidence was assessed by the GRADE approach. RESULTS: Our meta-analysis included 9 observational studies. The PCOS patients showed significantly higher NC values than the non-PCOS controls (SMD: 0.66, 95% CI: 0.41-0.91, p < 0.0001). In the bootstrap meta-analysis, the accuracy of the observed findings was proved (SMD = 0.66, 95% CI = 0.42-0.91) for the NC outcome. No publication bias was detected in the funnel plot analysis using Begg's and Egger's tests. The 95% prediction interval of 0.036-1.28 suggests that the true outcomes of the studies are generally in the same direction as the estimated average outcome. The sensitivity analysis provided the robustness of the outcome, and no single study was overly influential on the pooled estimate. CONCLUSION: This meta-analysis provides accurate evidence for significantly higher NC values in PCOS as compared to non-PCOS controls. There is no sufficient evidence on the diagnostic accuracy measures for NC in PCOS. Hence, further research on its diagnostic utility in PCOS is needed.

Unraveling the diversity and functions of sugar transporters for sustainable management of wheat rust.

Plant diseases threaten global food security by reducing the production and quality of produce. Identification of disease resistance sources and their utilization in crop improvement is of paramount significance. However, constant evolution and occurrence of new, more aggressive and highly virulent pathotypes disintegrates the resistance of cultivars and hence demanding the steady stream of disease resistance cultivars as the most sustainable way of disease management. In this context, molecular tools and technologies facilitate an efficient and rational engineering of crops to develop cultivars having resistance to multiple pathogens and pathotypes. Puccinia spp. is biotrophic fungi that interrupt crucial junctions for causing infection, thus risking nutrient access of wheat plants and their subsequent growth. Sugar is a major carbon source taken from host cells by pathogens. Sugar transporters (STPs) are key players during wheat-rust interactions that regulate the transport, exchange, and allocation of sugar at plant-pathogen interfaces. Intense competition for accessing sugars decides fate of incompatibility or compatibility between host and the pathogen. The mechanism of transport, allocation, and signaling of sugar molecules and role of STPs and their regulatory switches in determining resistance/susceptibility to rusts in wheat is poorly understood. This review discusses the molecular mechanisms involving STPs in distribution of sugar molecules for determination of rust resistance/susceptibility in wheat. We also present perspective on how detailed insights on the STP's role in wheat-rust interaction will be helpful in devising efficient strategies for wheat rust management.

Comparative transcriptome profiling of near isogenic lines PBW343 and FLW29 to unravel defense related genes and pathways contributing to stripe rust resistance in wheat.

Stripe rust (Sr), caused by Puccinia striiformis f. sp. tritici (Pst), is the most devastating disease that poses serious threat to the wheat-growing nations across the globe. Developing resistant cultivars is the most challenging aspect in wheat breeding. The function of resistance genes (R genes) and the mechanisms by which they influence plant-host interactions are poorly understood. In the present investigation, comparative transcriptome analysis was carried out by involving two near-isogenic lines (NILs) PBW343 and FLW29. The seedlings of both the genotypes were inoculated with Pst pathotype 46S119. In total, 1106 differentially expressed genes (DEGs) were identified at early stage of infection (12 hpi), whereas expressions of 877 and 1737 DEGs were observed at later stages (48 and 72 hpi) in FLW29. The identified DEGs were comprised of defense-related genes including putative R genes, 7 WRKY transcriptional factors, calcium, and hormonal signaling associated genes. Moreover, pathways involved in signaling of receptor kinases, G protein, and light showed higher expression in resistant cultivar and were common across different time points. Quantitative real-time PCR was used to further confirm the transcriptional expression of eight critical genes involved in plant defense mechanism against stripe rust. The information about genes are likely to improve our knowledge of the genetic mechanism that controls the stripe rust resistance in wheat, and data on resistance response-linked genes and pathways will be a significant resource for future research.

Sr65: a widely effective gene for stem rust resistance in wheat.

KEY MESSAGE: Sr65 in chromosome 1A of Indian wheat landrace Hango-2 is a potentially useful all-stage resistance gene that currently protects wheat from stem rust in Australia, India, Africa and Europe. Stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), threatened global wheat production with the appearance of widely virulent races that included TTKSK and TTRTF. Indian landrace Hango-2 showed resistance to Pgt races in India and Australia. Screening of a Hango-2/Avocet 'S' (AvS) recombinant inbred line population identified two stem rust resistance genes, a novel gene (temporarily named as SrH2) from Hango-2 and Sr26 from AvS. A mapping population segregating for SrH2 alone was developed from two recombinant lines. SrH2 was mapped on the short arm of chromosome 1A, where it was flanked by KASP markers KASP_7944 (proximal) and KASP_12147 (distal). SrH2 was delimited to an interval of 1.8-2.3 Mb on chromosome arm 1AS. The failure to detect candidate genes through MutRenSeq and comparative genomic analysis with the pan-genome dataset indicated the necessity to generate a Hango-2 specific assembly for detecting the gene sequence linked with SrH2 resistance. MutRenSeq however enabled identification of SrH2-linked KASP marker sunCS_265. Markers KASP_12147 and sunCS_265 showed 92% and 85% polymorphism among an Australian cereal cultivar diversity panel and can be used for marker-assisted selection of SrH2 in breeding programs. The effectiveness of SrH2 against Pgt races from Europe, Africa, India, and Australia makes it a valuable resource for breeding stem rust-resistant wheat cultivars. Since no wheat-derived gene was previously located in chromosome arm 1AS, SrH2 represents a new locus and named as SR65.

Allele mining in gene encoding fc fragment of IgG receptor, transporter, alpha (FCGRT) and association of nucleotide variants with passive transfer of immunity in neonatal buffalo calves.

BACKGROUND: Neonatal Fc receptors (FcRn) mediate the transcytosis of IgG present in colostrum across absorptive gut epithelium of newborn calves. FcRn receptor is a heterodimer composed of two polypeptides encoded by FCGRT (Fc fragment of IgG Receptor Transporter neonatal) and B2M (Beta 2 microglobulin) genes. Polymorphism in FCGRT gene may have a bearing on absorption of colostral immunoglobulins by neonatal buffalo calves, thereby affecting their immune status and susceptibility to diseases. The primary aim of our study was to mine alleles and single nucleotide polymorphs in the FCGRT gene and determine their association with the levels of IgG in serum of neonatal buffalo calves. METHODS AND RESULTS: On the basis of serum IgG levels estimated by indirect ELISA in 80 newborn calves, 20 calves each with highest and lowest IgG concentration were selected to study polymorphism in the FCGRT gene. The exonic regions of this gene were amplified in nine fragments which were subjected to PCR-SSCP to detect variations followed by the sequencing of variants to locate the SNPs. A total of nine SNPs (7 in introns and 2 in exons) were detected in four polymorphic fragments. Association study based on Odds ratios (ORs) with 95% Confidence Interval (CIs) established that the SNP G40T in fragment 3 has a significant (P < 0.05) bearing on IgG level in serum of neonatal buffalo calves. CONCLUSION: Genetic variation in FCGRT gene in buffalo calves was found to be associated with their serum IgG levels in neonatal stage which may have implications in calf survival and growth vis-à-vis inadequate transfer of passive immunity.

Allelic to genome wide perspectives of swine genetic variation to litter size and its component traits.

Litter size is a complex and sex limited trait that depends on various biological, managemental and environmental factors. Owing to its low heritability it is inefficaciously selected by traditional methods. However, due to higher heritability of ovulation rate and embryo survival, selection based on component traits of litter size is advocated. QTL analysis and candidate gene approach are among the various supplementary/alternate strategies for selection of litter size. QTL analysis is aimed at identifying genomic regions affecting trait of interest significantly. Candidate gene approach necessitates identification of genes potentially affecting the trait. There are various genes that significantly affect litter size and its component traits viz. ESR, LEP, BF, IGFBP, RBP4, PRLR, CTNNAL1, WNT10B, TCF12, DAZ, and RNF4. These genes affect litter size in a complex interacting manner. Lately, genome wide association study (GWAS) have been utilized to unveil the genetic and biological background of litter traits, and elucidate the genes governing litter size. Favorable SNPs in these genes have been identified and offers a scope for inclusion in selection programs thereby increasing breeding efficiency and profit in pigs. The review provides a comprehensive coverage of investigations carried out globally to unravel the genetic variation in litter size and its component traits in pigs, both at allelic and genome wide level. It offers a current perspective on different strategies including the profiling of candidate genes, QTLs, and genome wide association studies as an aid to efficient selection for litter size and its component traits.

Anaerobic digestion as a sustainable technology for efficiently utilizing biomass in the context of carbon neutrality and circular economy.

Carbon emissions and associated global warming have become a threat to the world, the major contributor being the extensive use of fossil fuels and uncontrolled generation of solid wastes. Energy generation from renewable energy sources is considered an alternative to achieving carbon neutrality. Anaerobic digestion (AD) is a sustainable technology that has been endorsed as a low-carbon technology complimenting both waste management and renewable energy sectors. The AD technology recovers the volatile matter from waste biomass as much as possible to produce biogas, thus reducing carbon emission as compared to open dumping or burning. However, there is a need of compilation of information on how each subsystem in AD contributes to the overall carbon neutrality of the entire system and chances of achieving a circular economy along with it. Therefore, this article aims to clarify the associated internal and external factors that determine the low carbon characteristic of anaerobic digestion technology. From this review, the potential of AD system for energy-atmosphere-agriculture nexus has been explored. Carbon emission mapping of the potential entities involved in AD were identified and perspective to life cycle assessment and future research direction has been pointed out. Climate change impact and acidification potential are the two entities that can influence the overall environmental sustainability of an AD system. It was recognized that each stage of AD system starting from substrate supply chain, biogas production, upgradation, utilization, and digestate application had a remarkable effect on the overall carbon emission potential based on its design, operation, and maintenance. Selection of suitable substrates and co-digesting them together for improved biogas production rate with high methane content and proper digestate post-processing and storage can vastly reduce the carbon emission potential of the AD technology. Further, a case scenario of India was assessed considering the utilization of major surplus biomass available through AD. Re-routing the three major substrates such as agricultural crop residues, animal wastes and organic fraction of municipal solid wastes through AD can reduce at least 3.5-3.8 kg CO2-eq per capita of annual carbon emission load in India. Furthermore, the pathways in which the policy and legislations over establishment of AD technology and how to explore linkages between achieving circular economy and low carbon economy for Indian scenario has been highlighted.

Methanolic fraction of Cassia fistula L. bark exhibits potential to combat oxidative stress and possess antiproliferative activity.

Cassia fistula L. is well known for its traditional medicinal properties as an anti-inflammatory, hepatoprotective, antifungal, antibacterial, antimutagenic, and wound healing agent. The aim of the present study was to determine antioxidant, genoprotective, and cytotoxic potential of different fractions of C. fistula bark including hexane (CaMH), chloroform (CaMC), ethyl acetate (CaME), and methanol (CaMM). Among all the fractions studied, CaMM exhibited maximal radical scavenging activity in antioxidant DPPH assay, Superoxide anion radical scavenging assay and nitric oxide radical scavenging assay displayed an IC50 value of 18.95, 29.41, and 13.38 µg/ml, respectively. CaMM fraction possessed the highest phenolic (130.37 mg gallic acid equivalent/g dry weight of extract) and flavonoid (36.96 mg rutin equivalent/g dry weight of fraction) content. Data demonstrated significant positive correlation between polyphenol levels and radical scavenging activity. Single cell gel electrophoresis (Comet assay) exhibited genoprotective potential of C. fistula bark fractions against DNA damage induced by hydrogen peroxide (H2O2) in human lymphocytes. CaMM fraction displayed highest protective ability against H2O2 induced-toxicity as evidenced by significant decrease in % tail DNA content from 30 to 7% at highest concentration (200 µg/ml). CaMM was found to be rich in catechin, gallic acid, chlorogenic acid, and kaempferol. The phenolic content and antioxidant ability of the fractions was markedly negatively correlated with H2O2- induced DNA damage in human lymphocytes. Cytotoxic potential was evaluated against dermal epidermoid carcinoma (A431), pancreatic (MIA PaCa-2) and brain glioblastoma (LN-18) cancer cell lines using MTT assay. Results showed that C. fistula bark fractions possessed highest toxicity against the skin carcinoma cells. CaMM fraction reduced over 50% cell growth at the concentration of 76.72 µg/ml in A431 cells. These findings suggest that fractions of C. fistula bark exhibit potential to be considered as therapeutic agents in various carcinomas.

Estimation of microsatellite-based autozygosity and its correlation with pedigree inbreeding coefficient in crossbred cattle.

In countries where farming is largely subsistence, no pedigree records of farm animals are maintained at farmers' herd and scientific mating plans are not observed which leads to the accumulation of inbreeding and loss of production potential. Microsatellites have been widely used as reliable molecular markers to measure inbreeding. We attempted to correlate autozygosity estimated from microsatellite data with the inbreeding coefficient (F) calculated from pedigree data in Vrindavani crossbred cattle developed in India. The inbreeding coefficient was calculated from the pedigree of ninety-six Vrindavani cattle. Animals were further grouped into three groups viz. acceptable/low (F: 0-5%), moderate (F: 5-10%) and high (F: ≥10%), based on their inbreeding coefficients. The overall mean of the inbreeding coefficient was found to be 0.070 ± 0.007. A panel of twenty-five bovine-specific loci were chosen for the study according to ISAG/FAO. The mean FIS, FST, and FIT values were 0.0548 ± 0.025, 0.012 ± 0.001 and 0.0417 ± 0.025, respectively. There was no significant correlation between the FIS values obtained and the pedigree F values. The locus-wise individual autozygosity was estimated using the method-of-moments estimator (MME) formula for locus-specific autozygosity. The autozygosities ascribing to CSSM66 and TGLA53 were found to be significantly (p < .01 and p < .05, respectively) correlated with pedigree F values.

Design, development and characterisation of an optimised scaffold to enhance cell proliferation for tissue repair.

Scaffolds are implanted to spur the regeneration of damaged tissues. The inappropriate construction of scaffolds laden with cells is not efficient. The optimisation of the scaffolds' constituents is essential for tissue repair. In this study, a scaffold embedded with Raloxifene drug was optimised via Response Surface Methodology (RSM), targeting controlled cell proliferation. The independent variables for RSM (fibronectin, collagen I, glutaraldehyde, and Raloxifene) were screened in Swiss target prediction software (probability ≥99%) to optimise dependent variables (porosity, cell viability, degradation, and swelling) by ANOVA and characterised with FTIR, SEM and contact angle measurement. The scaffold was tested for antimicrobial property, and proliferation and attachment of mouse mesenchymal stem cells. The ANOVA analysis with p value ≤ 0.0001 suggested the optimal concentration of biomaterials and drugs. The optimised scaffold displayed 80% porosity with pore size 33 ± 3 µm. We also observed significant cell attachment and proliferation (p value ≤ 0.05) in optimised scaffold. The scaffold may be further evaluated for its potential for tissue repair.

Platelet-rich plasma: a comparative and economical therapy for wound healing and tissue regeneration.

Rise in the incidences of chronic degenerative diseases with aging makes wound care a socio-economic burden and unceasingly necessitates a novel, economical, and efficient wound healing treatment. Platelets have a crucial role in hemostasis and thrombosis by modulating distinct mechanistic phases of wound healing, such as promoting and stabilizing the clot. Platelet-rich plasma (PRP) contains a high concentration of platelets than naïve plasma and has an autologous origin with no immunogenic adverse reactions. As a consequence, PRP has gained significant attention as a therapeutic to augment the healing process. Since the past few decades, a robust volume of research and clinical trials have been performed to exploit extensive role of PRP in wound healing/tissue regeneration. Despite these rigorous studies and their application in diversified medical fields, efficacy of PRP-based therapies is continuously questioned owing to the paucity of large samplesizes, controlled clinical trials, and standard protocols. This review systematically delineates the process of wound healing and involvement of platelets in tissue repair mechanisms. Additionally, emphasis is laid on PRP, its preparation methods, handling, classification,application in wound healing, and PRP as regenerative therapeutics combined with biomaterials and mesenchymal stem cells (MSCs).

Analysis and approach to renal trauma: A five-year experience at a level I trauma centre in north India.

PURPOSE: Renal trauma constitutes 0.5% - 5% of all trauma patients, and 10% - 20% of abdominal trauma. It is the most commonly injured organ in the genitourinary tract. Road traffic crash (RTC) is the most common cause. In recent years due to the advances in radiological imaging and endovascular techniques, there has been an increase in the nonoperative management of renal trauma. We investigated a large trauma cohort at a level I trauma centre to evaluate patients' demographics with renal trauma, their management, and the outcomes. METHODS: This was a retrospective analysis of the prospectively collected data of renal trauma patients managed from January 2016 to December 2020. Patients who visited the level I trauma centre in north India with renal trauma were included in this study. Patients who were dead on arrival in the emergency department were excluded. Demographics, mechanism of injury, presence of hemorrhagic shock, associated injuries, complications, length of hospital stay (LOS), discharge, and mortality were recorded. The data were entered in Microsoft Excel 365 and analysed using SPSS version 21. RESULTS: This study collected data from 303 renal trauma patients. Males constituted 86.5% of the patients. Most patients were young, aged from 20 - 40 years. Blunt renal trauma was the predominant mode of injury (n = 270, 89.1%). RTCs (n = 190, 62.7%) and falls from height (n = 65, 21.4%) were the 2 most common mechanisms of injury. Focused assessment with sonography in trauma was positive in 68.4% of patients. Grade III (grading by the American Association for the Surgery of Trauma) renal trauma (30.4%) was the most common grade in our study. The liver (n = 104, 34.3%) and splenic trauma (n = 96, 31.7%) were the most commonly associated injuries. Of the 303 patients, 260 (85.8%) were managed nonoperatively. The mean (SD) of the patients' LOS was 12.5 (6.5) days. There were 25 (8.3%) mortalities during the study period and all of them had associated other injuries. The comparison of LOS of isolated renal trauma group and renal trauma with associated injuries group was not statistically significant (p = 0.322). All the patients who died during the study period had renal trauma with associated other organ injuries. None of the patients with isolated renal trauma died during the study. The outcome comparison between both groups was not statistically significant (p = 0.110). CONCLUSION: Renal trauma predominantly occurs in young males, especially due to RTCs followed by fall from height. Focused assessment with sonography in trauma is not reliable in detecting renal injuries, other diagnostic tools such as contrast enhanced computed tomography torso should be considered in diagnosing and grading these injuries. Renal trauma usually does not occur in isolation. Majority are associated with other abdominal and extra abdominal injuries. Most of the times these injuries can be managed nonoperatively, which can achieve a low mortality. The patients who required surgery had high mortality as compared to patients who managed nonoperatively. These patients who required surgery had either severe renal or extra renal trauma and were in hemorrhagic shock. Renal trauma from this large cohort may contribute to improving the quality of care for patients with renal trauma by obtaining knowledge about the patient's characteristics, management, and outcomes.