Immunomodulatory Effects of a Herbo-Mineral Ayurvedic Formulation in Experimental Models.

BACKGROUND: Ayurveda, an ancient Indian system of medicine, encapsulates comprehensive principles and formulations for disease prevention and treatment. A herbo-mineral Ayurvedic formulation, IMMBO, comprising Mandoor Bhasma and 18 herbs has shown promising results in treating allergic rhinitis in clinical studies. OBJECTIVE: This discussed series of experimental studies were conducted to explore the immuno-modulatory potential of IMMBO. METHODOLOGY: A series of experimental studies were carried out in immunosuppressed rats to explore the immune-modulatory effects of IMMBO. RESULTS: IMMBO was effective in reinstating neutrophil activation, stimulating cellular and humoral immunity, and counteracting immunosuppression at the molecular level. The modulation of key signalling molecules, including tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 beta (IL-1ß), extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), and nuclear factor-kappa B (NF-κb), showcased the formulation's multifaceted impact. Additionally, its ability to block histamine release suggests potential in controlling allergic states, positioning it as a promising therapeutic candidate for immune-related disorders. However, the precise mode of action remains elusive, warranting further in-depth pharmacological studies. CONCLUSION: This research substantiates the ancient Ayurvedic wisdom using modern scientific parameters, endorsing IMMBO's potential as an immune-modulatory agent.

Novel insights into drought-induced regulation of ribosomal genes through DNA methylation in chickpea.

Modifications within the epigenome of an organism in response to external environmental conditions allow it to withstand the hostile stress factors. Drought in chickpea is a severely limiting abiotic stress factor which is known to cause huge yield loss. To analyse the methylome of chickpea in response to drought stress conditions and how it affects gene expression, we performed whole-genome bisulfite sequencing (WGBS) and RNA-seq of two chickpea genotypes which contrast for drought tolerance. It was observed that the mCHH was most variable under drought stress and the drought tolerant (DT) genotype exhibited substantial genome-wide hypomethylation as compared to the drought sensitive (DS) genotype. Specifically, there was substantial difference in gene expression and methylation for the ribosomal genes for the tolerant and sensitive genotypes. The differential expression of these genes was in complete agreement with earlier reported transcriptomes in chickpea. Many of these genes were hypomethylated (q < 0.01) and downregulated under drought stress (p < 0.01) in the sensitive genotype. The gene RPS6 (ribosomal protein small subunit) was found to be downregulated and hypomethylated in the drought sensitive genotype which could possibly lead to reduced ribosomal biosynthesis. This study provides novel insights into regulation of drought-responsive genes in chickpea.

Proof of Efficacy Study to Evaluate an Ayurvedic Formulation in the Treatment of Allergic Rhinitis: An Open Label Randomized Controlled Clinical Trial.

BACKGROUND: Allergic rhinitis is largely treated by using antihistamines and nasal sprays, either alone or in combination. However, these measures ease out the symptoms but do not address causative factors, and have their share of side effects and limitations. An Ayurvedic herbo-mineral formulation, IMMBO, has been reported to be effective in treating allergic rhinitis. OBJECTIVE: The present study was carried out to evaluate the efficacy, safety, and tolerability of the Ayurvedic herbo-mineral formulation in comparison with a fixed-dose combination of levocetirizine and montelukast. METHOD: This was a randomized, comparative, clinical study carried out on 250 patients at a medical college in India. The patients were enrolled according to the eligibility criteria of the study and randomized into two groups, to receive either Ayurvedic herbo-mineral formulation, IMMBO, or a combination of levocetirizine and montelukast for 28 days. Total nasal symptom score (TNSS) and Immunoglobulin E (IgE) were calculated for evaluation of efficacy parameters.  Result: At the end of therapy both IMMBO and levocetirizine and montelukast combination showed significant improvement in TNSS in both treated population and per protocol population. The IMMBO group had a statistically higher reduction in TNSSs compared to the levocetirizine + montelukast group (-5.70 vs. -3.31; p<0.01). There was a statistically significant difference in the reduction of IgE levels between the groups (-351.54 vs. -208.79; p<0.05).  Conclusion: The findings of this study establish prima facie evidence about the efficacy and safety of Ayurvedic formulation. However, the said Ayurvedic formulation needs to be further developed scientifically.

Unravelling the due importance of pseudogenes and their resurrection in plants.

The complexities of a genome are underpinned to the vast expanses of the intergenic region, which constitutes ∼97-98% of the genome. This region is essentially composed of what is colloquially referred to as the "junk DNA" and is composed of various elements like transposons, repeats, pseudogenes, etc. The latter have long been considered as dead elements merely contributing to transcriptional noise in the genome. Many studies now describe the previously unknown regulatory functions of these genes. Recent advances in the Next-generation sequencing (NGS) technologies have allowed unprecedented access to these regions. With the availability of whole genome sequences of more than 788 different plant species in past 20 years, genome annotation has become feasible like never before. Different bioinformatic pipelines are available for the identification of pseudogenes. However, still little is known about their biological functions. The functional validation of these genes remains challenging and research in this area is still in infancy, particularly in plants. CRISPR/Cas-based genome editing could provide solutions to understand the biological roles of these genes by allowing creation of precise edits within these genes. The possibility of pseudogene reactivation or resurrection as has been demonstrated in a few studies might open new avenues of genetic manipulation to yield a desirable phenotype. This review aims at comprehensively summarizing the progress made with regards to the identification of pseudogenes and understanding their biological functions in plants.

Genetic mapping of quantitative trait loci associated with drought tolerance in chickpea (Cicer arietinum L.).

Elucidation of the genetic basis of drought tolerance is vital for genomics-assisted breeding of drought tolerant crop varieties. Here, we used genotyping-by-sequencing (GBS) to identify single nucleotide polymorphisms (SNPs) in recombinant inbred lines (RILs) derived from a cross between a drought tolerant chickpea variety, Pusa 362 and a drought sensitive variety, SBD 377. The GBS identified a total of 35,502 SNPs and subsequent filtering of these resulted in 3237 high-quality SNPs included in the eight linkage groups. Fifty-one percent of these SNPs were located in the genic regions distributed throughout the genome. The high density linkage map has total map length of 1069 cm with an average marker interval of 0.33 cm. The linkage map was used to identify 9 robust and consistent QTLs for four drought related traits viz. membrane stability index, relative water content, seed weight and yield under drought, with percent variance explained within the range of 6.29%-90.68% and LOD scores of 2.64 to 6.38, which were located on five of the eight linkage groups. A genomic region on LG 7 harbors quantitative trait loci (QTLs) explaining > 90% phenotypic variance for membrane stability index, and > 10% PVE for yield. This study also provides the first report of major QTLs for physiological traits such as membrane stability index and relative water content for drought stress in chickpea. A total of 369 putative candidate genes were identified in the 6.6 Mb genomic region spanning these QTLs. In-silico expression profiling based on the available transcriptome data revealed that 326 of these genes were differentially expressed under drought stress. KEGG analysis resulted in reduction of candidate genes from 369 to 99, revealing enrichment in various signaling pathways. Haplotype analysis confirmed 5 QTLs among the initially identified 9 QTLs. Two QTLs, qRWC1.1 and qYLD7.1, were chosen based on high SNP density. Candidate gene-based analysis revealed distinct haplotypes in qYLD7.1 associated with significant phenotypic differences, potentially linked to pathways for secondary metabolite biosynthesis. These identified candidate genes bolster defenses through flavonoids and phenylalanine-derived compounds, aiding UV protection, pathogen resistance, and plant structure.The study provides novel genomic regions and candidate genes which can be utilized in genomics-assisted breeding of superior drought tolerant chickpea cultivars.

The SPL transcription factor genes are potential targets for epigenetic regulation in response to drought stress in chickpea (C. arietinum L.).

BACKGROUND: Crop improvement for tolerance to various biotic and abiotic stress factors necessitates understanding the key gene regulatory mechanisms. One such mechanism of gene regulation involves changes in cytosine methylation at the gene body and flanking regulatory sequences. The present study was undertaken to identify genes which might be potential targets of drought-induced DNA methylation in chickpea. METHODS AND RESULTS: Two chickpea genotypes, which contrast for drought tolerance, were subjected to drought stress conditions and their differential response was studied by analysing different morpho-physiological traits. Utilizing the in-house, high throughput sequencing data, the SQUAMOSA promoter-binding (SBP) protein-like (SPL) transcription factor genes were identified to be differentially methylated and expressed amongst the two genotypes, in response to drought stress. The methylation status of one of these genes was examined and validated through bisulfite PCR (BS-PCR). The identified genes could be possible homologs to known epialleles and can therefore serve as potential epialleles which can be utilized for crop improvement in chickpea. CONCLUSION: The SPL TF genes are potential targets of epigenetic regulation in response to drought stress in chickpea. Since these are TFs, they might play important roles in controlling the expression of other genes, thus contributing to differential drought response of the two genotypes.

Genome-wide identification, in silico characterization and expression analysis of the RNA helicase gene family in chickpea (C. arietinum L.).

The RNA helicases are an important class of enzymes which are known to influence almost every aspect of RNA metabolism. The majority of RNA helicases belong to the SF2 (superfamily 2) superfamily, members of which are further categorized into three separate subfamilies i.e., the DEAD, DEAH and DExD/H-box subfamilies. In chickpea, these RNA helicases have not been characterized until now. A genome-wide analysis across the chickpea genome led to the identification of a total of 150 RNA helicase genes which included 50 DEAD, 33 DEAH and 67 DExD/H-box genes. These were distributed across all the eight chromosomes, with highest number on chromosome 4 (26) and least on chromosome 8 (8). Gene duplication analysis resulted in identification of 15 paralogous gene pairs with Ka/Ks values < 1, indicating towards the genes being under purifying selection during the course of evolution. The promoter regions of the RNA helicase genes were enriched in cis-acting elements like the light and ABA-responsive elements. The drought responsiveness of the genes was analysed by studying the expression profiles of few of these genes, in two different genotypes, the cultivated variety ICC 8261 (kabuli, C. arietinum) and the wild accession ILWC 292 (C. reticulatum), through qRT-PCR. These genotypes were selected based on their drought responsiveness in a field experiment, where it was observed that the percentage (%) reduction in relative water content (RWC) and membrane stability index (MSI) for the drought stressed plants after withholding water for 24 days, over the control or well-watered plants, was least for both the genotypes. The genes CaDEAD50 and CaDExD/H66 were identified as drought-responsive RNA helicase genes in chickpea. The protein encoded by the CaDExD/H66 gene shares a high degree of homology with one of the CLSY (CLASSY) proteins of A. thaliana. We hypothesize that this gene could possibly be involved in regulation of DNA methylation levels in chickpea by regulating siRNA production, in conjunction with other proteins like the Argonaute, RNA dependent RNA polymerases and Dicer-like proteins.

Genome-wide identification and expression analysis of the GRAS gene family in response to drought stress in chickpea (Cicer arietinum L.).

The GRAS (gibberellic acid insensitive, repressor of GAI and scarecrow) transcription factors (TFs) regulate diverse biological processes involved in plant growth and development. These TFs are also known to regulate gene expression in response to various abiotic stress factors like cold, drought, etc. In chickpea one of the most devastating abiotic stress factors is terminal drought. The GRAS TF family has not been characterized in chickpea (Cicer arietinum L.) until now. In this study, we report 46 GRAS TF genes (CaGRAS genes) in the chickpea genome. The CaGRAS proteins were categorized into nine subfamilies based on their phylogenetic relationship with known GRAS members of Arabidopsis and soybean. The PAT subfamily was the largest consisting of ten CaGRAS members whereas the LAS subfamily was the smallest with only one member. Gene duplication analysis revealed that segmental duplication was the primary reason for the expansion of this gene family within the chickpea genome. The gene expression levels of CaGRAS genes were analysed using two different chickpea varieties contrasting for drought tolerance trait, i.e., ICC 4958 (drought tolerant) and ICC 1882 (drought sensitive). On exposure to drought stress, the two chickpea genotypes, exhibited differential drought response, which was quantified and estimated in terms of differences in leaf relative water content (RWC). The well-watered or control plants of the drought tolerant variety were able to maintain a higher leaf RWC by the end of the drought stress period, whereas the control plants of the drought sensitive variety continued to show a decline in leaf RWC. The two genotypes also differed in their root morphologies, under well-watered and drought stress conditions. The gene expression analysis revealed a potential role of PAT, SCR, SCL3 and SHR GRAS members in the regulation of differential response to drought, in the root tissues, for both the genotypes. CaGRAS 12 (SCR) was identified as a drought-responsive GRAS TF gene, which could serve as a potential candidate gene for utilization in developing chickpea varieties with improved drought tolerance. This study demonstrates the drought-responsive expression of CaGRAS genes in chickpea and also describes the morpho-physiological response of chickpea plants to drought stress conditions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03104-z.

Respiratory health of workers exposed to polyacrylate dust.

BACKGROUND: Polyacrylate (PA) powder dust formed in PA manufacturing units is fine sized, i.e., in nanosize. Although several previous studies reported possible significant adverse effects of nanomaterials, studies on the harmful effect of small-sized PA particles on the respiratory health of the workers are scarce. The present study was carried out to assess the effect of PA on respiratory health and lung volumes/rates among the workers of PA manufacturing unit. MATERIALS AND METHODS: The present cross-sectional study included 84 workers of PA manufacturing unit. Using interview technique as a tool for data collection, demographic, occupational, and clinical details of the workers were recorded on the predesigned pro forma. This was followed by detailed clinical examination, spirometry, chest X-ray ( posteroanterior [PA] view), and high-resolution computed tomography (HRCT) examination of each worker. RESULTS: On the basis of clinical examination, chest radiography, and HRCT, 17.9% of the workers were found to have fibrotic and cavitary changes in lung parenchyma. The production department workers had a higher proportion of respiratory morbidities as compared to supervisory or office staff. Age, gender, smoking habit, and duration of exposure were nonsignificant risk factors for respiratory morbidity. The overall mean forced vital capacity, forced expiratory volume in 1st s, Peak Expiratory Flow Rate (PEFR), (Maximal Mid Expiratory Flow Rate) MMEFR0.2-1.2, and MMEFR25%-75% were 3.19 ± 0.77 L, 2.72 ± 0.67 L, 6.82 ± 1.86 L/s, 5.79 ± 2.03 L/s, and 3.16 ± 1.19 L/s, respectively. Females and those having respiratory morbidity had significantly lower values of all spirometric parameters as compared to their counterparts. CONCLUSIONS: The workers exposed to engineered fine dust of PA may be at risk of respiratory ill-health.

Polymorphism of CYP1A1 gene variants rs4646903 and rs1048943 relation to the incidence of cervical cancer in Chhattisgarh.

Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls). All subjects were genotyped for CYP1A1m1 (T>C) and m2 (A>G) using PCR-RFLP with statistical analysis by using SPSS version 16.0 and VassarStats (online). Among the two gene variants rs4646903 (T>C) and rs1048943 (A>G), individuals with AG and GG genotypes of CYP1A1m2 polymorphism have significantly higher and increased risk of cervical cancer (OR=2.0, 95%CI=1.04-3.84, p=0.035; OR=62.9, 95%CI=3.72-1063.83, p=0.004 respectively) and the association of CYP1A1m1 polymorphism did not show any significant relationship with cervical cancer patients (p=0.23). The 'G' allele showed strong association with the disease (p<0.0001). Thus, CYP1A1m2 polymorphism showed an increased risk in the population leading to cervical cancer. Our study suggested that the presence of 'C' allele of rs4646903 (T>C) showed no risk and 'G' allele of rs1048943 (A>G) might be a leading allele to cause increased cervical cancer susceptibility due to significant association of CYP1A1m2 gene polymorphism.

Redundant Design in Interdependent Networks.

Modern infrastructure networks are often coupled together and thus could be modeled as interdependent networks. Overload and interdependent effect make interdependent networks more fragile when suffering from attacks. Existing research has primarily concentrated on the cascading failure process of interdependent networks without load, or the robustness of isolated network with load. Only limited research has been done on the cascading failure process caused by overload in interdependent networks. Redundant design is a primary approach to enhance the reliability and robustness of the system. In this paper, we propose two redundant methods, node back-up and dependency redundancy, and the experiment results indicate that two measures are effective and costless. Two detailed models about redundant design are introduced based on the non-linear load-capacity model. Based on the attributes and historical failure distribution of nodes, we introduce three static selecting strategies-Random-based, Degree-based, Initial load-based and a dynamic strategy-HFD (historical failure distribution) to identify which nodes could have a back-up with priority. In addition, we consider the cost and efficiency of different redundant proportions to determine the best proportion with maximal enhancement and minimal cost. Experiments on interdependent networks demonstrate that the combination of HFD and dependency redundancy is an effective and preferred measure to implement redundant design on interdependent networks. The results suggest that the redundant design proposed in this paper can permit construction of highly robust interactive networked systems.

Risk of bias in randomized trials of pharmacological interventions in children and adults.

OBJECTIVE: To determine whether randomized controlled trials of pharmacologic interventions in children are more likely to be biased than similar trials in adults. STUDY DESIGN: Trials involving only children and published in MEDLINE between January 2008 and October 2009 (n=100) were randomly selected and matched, by drug class and therapeutic area, with a similar trial completed in adults. The Cochrane risk of bias tool was used to compare the pediatric and adult trials. RESULTS: The characteristics of adult and pediatric trials included were similar, except that adult studies were more likely to be conducted in Europe and published in specialty journals. Two-thirds of all trials were single center, and 62% had 100 or fewer participants. Many trials had an unclear risk of bias for allocation concealment (65% adult, 52% pediatric). More pediatric trials had a low risk of bias for random sequence generation (59% pediatric, 41% adult, P=.002) and blinding of outcome assessment (63% pediatric, 48% adult, P=.04) than adult trials; however, a sensitivity analysis of trials published since 2008 (and so matched by year of publication) did not confirm this finding, suggesting year of publication was an important confounder. CONCLUSIONS: When randomized controlled trials are matched for drug class and therapeutic area, trials involving children display a similar risk of bias. Differences in the risk of bias between pediatric and adult trials are not caused by differences in the capacity of researchers to conduct and report trials of high quality.

A national study of the processes and outcomes of paediatric formulary applications in Australia.

OBJECTIVE: To evaluate the processes by which pharmaceuticals are added to the formularies of Australian paediatric hospitals. DESIGN: Descriptive study of the processes and outcomes of all submissions to Australian paediatric hospital drug and therapeutics committees from 1 July 2010 to 31 December 2011. SETTING: All eight tertiary paediatric hospitals in Australia. PARTICIPANTS: Interviews with committee secretaries or delegates and document analysis. MAIN OUTCOME MEASURES: Total number of formulary applications, stratified by therapeutic class, approval rates for each hospital and quality of supporting information. RESULTS: One hundred and twenty applications were considered during the study period, with most applications approved (range, 67%-100%). Neurological agents were the most common therapeutic class considered. A conflict of interest was declared for 10 applications (8%). Forty-five (38%) were independently reviewed by a statewide medicines advisory committee or hospital pharmacist. Several committees approved identical applications during the period of review and with different outcomes. For applications submitted for new drugs or new indications (95 applications), supporting data included randomised controlled trials (37/95), case series (36/95), product information (34/95) and narrative reviews (29/95). Few applications (14/95) included a systematic review or meta-analysis. No application included an evaluation of the risk of bias of supporting studies. CONCLUSIONS: There is limited high-quality evidence informing paediatric hospital-based drug approvals. Approval processes vary considerably among institutions with substantial duplication of effort and variable outcomes. Resources and training appear insufficient given the technical complexity of submissions. A national, standardised approach to hospital-based drug evaluation could reduce overlap and improve decision making.

Empathy and personality traits as predictors of adjustment in Indian youth.

BACKGROUND: Although adjustment has been studied in relation with a host of variables, the relevance of empathy and its importance in the process of adjustment has received little attention. It is a well-known fact that personality plays a very important role in our interactions and dealings and also that empathy facilitates this process. SETTINGS AND DESIGN: This study evaluated whether these two things combined together affect or predict adjustment. A random sample of 52 young male adults volunteered for this study. MATERIALS AND METHODS: These 52 male participants filled up questionnaires related to personality (The Jackson Personality Inventory), empathy. The Empathy Quotient) and adjustment (Bell adjustment inventory). ANALYSIS AND RESULTS: The data were analyzed using correlation and regression analysis. Personality traits like interpersonal affect, conformity facilitated the process of adjustment, whereas traits like anxiety worked in the opposite direction. Empathy also emerged as a significant contributor to the social adjustment. CONCLUSIONS: Results showed that both empathy and personality traits accounted for unique variance in adjustment. Results are discussed in terms of empathy, personality traits and their role in adjustment.

Salmonella enterica enteritidis arthritis following trauma in a child with thalassemia major.

Osteoarticular infections caused by Non-typhi Salmonella are exceptionally encountered. We report a case of a bacteriologically documented knee joint infection due to Salmonella enterica serotype enteritidis, following trauma in a child with thalassemia major. Emergency arthrotomy combined with antimicrobial therapy was helpful in eradication of infection. Physicians should be aware of this rare manifestation of Non-typhi Salmonella infections in thalassemic patients.

Caroli's syndrome with ureterovesical calculi in a young child.

An 18-month-old boy was admitted with fever, abdominal pain, and hepatomegaly. CT scan revealed dilatation of intrahepatic biliary radicals with central dot sign, bilateral nephrocalcinosis, multiple ureteric and urinary bladder stones and right-sided obstructive hydroureteronephrosis due to a ureterovesical calculus of about 1.5 cm. Liver biopsy showed early hepatic fibrosis.

Carcinoma developing in a fibroadenoma in a woman with a family history of breast cancer: a case report and review of literature.

INTRODUCTION: Malignant transformation of a fibroadenoma is rare with only about 100 cases reported in the world literature. Fibroadenoma occurring in middle aged woman with a strong family history of breast or ovarian cancer should be investigated with a high suspicion for malignancy. CASE PRESENTATION: A 35-year- old Indian lady operated previously for fibroadenoma of the right breast presented with a recurrent lump at the same site. She had a strong family history of breast carcinoma. Mammography and trucut biopsy was suggestive of infiltrating duct carcinoma. She was managed by lumpectomy and axillary lymph node dissection with a satisfactory outcome. There was no evidence of BRCA-1, BRCA-2 mutation on immunohistochemistry. CONCLUSION: Malignant change in a pre-existing fibroadenoma is rare, however in a middle aged woman with a family history of breast cancer it should be suspected. In the absence of any definite clinical and radiological criteria of diagnosing malignant change in a fibroadenoma, high suspicion index is mandatory. The management and outcome depends on the stage and grade of presentation.

Respiratory health of female stone grinders with free silica dust exposure in Gujarat, India.

Eighty-five female quartz mill stone-grinding workers belonging to the Naika, Rathwa and Damor tribes of Chhotaudepur village of the Godhra region of Gujarat, Western India were surveyed and examined to assess health effects related to free silica dust exposure. The mean age for the subjects was 28.2 +/- 9.2 years, while the mean duration of exposure was 2.04 +/- 1.7 years. Chest radiographs showed findings suggestive of silicosis in 14%, silico-tuberculosis in 11.6% and tuberculosis in 8.1% of the study subjects. Respiratory morbidity was significantly associated with duration of exposure (X2 = 9.9, df = 2, p<0.007). On spirometry, obstructive, restrictive and combined (restrictive as well as obstructive) changes were found in 12.8%, 10.5% and 3.5% of the subjects, respectively. Overall, about one-third of subjects displayed abnormal pulmonary function and respiratory morbidity on chest radiographs.