Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.

Chronic cervical spondylitis (CCS), a degenerative disorder of the spine, is known for causing disability among old and young people. Single-nucleotide polymorphisms (SNPs) in various cytokine genes have demonstrated an impactful association with several inflammatory disorders. In the present study, we have investigated the SNPs and allelic distribution of the three most prevalent cytokines genes, IL-1β (-511C/T), TNF-α (-308G/A), and TGF-β (-509C/T), along with serum levels of these cytokines in 252 subjects. SNPs were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and digested fragments were separated and visualized using agarose gel electrophoresis and Native Polyacrylamide gel electrophoresis (PAGE). The serum cytokine levels were analyzed with a flow cytometer using a customized multiplex bead-based assay. It was observed that these SNPs did not reflect the susceptibility to CCS but were associated with susceptibility to CCS. We found a significant association between the C/C and G/G genotypes and the C and G alleles of IL-1β and TNF-α, respectively, suggesting a lower risk of CCS. The frequency distribution of risk alleles (-511T) and (-308A) were simultaneously higher in CCS compared to the control, reflecting the susceptibility to CCS. TGF-β showed a significant association with disease susceptibility, along with a significant correlation between age and the chronicity of CCS. The serum cytokine levels were significantly different in CCS and controls.

We have attempted to summarize the efficacy of bacteriophage therapy, highlighting the recent advances and phage delivery methods in different clinical trials and animal studies for wound-associated infections. Bacteriophage therapy is the lyse of bacteria by bacteriophages at the site of invasion. As bacteria become more resistant to antibiotics, discovering an alternative is more important than ever, and bacteriophage therapy has yielded promising outcomes. A clear knowledge of the bacteriophage, microbiota, and human host and their interaction is necessary to implement bacteriophage treatment on a large scale. Much technological advancement and regulatory guidelines increased the credibility of phage therapy (PT). Still, the challenges include the development of efficient bacteriophage screening methods, phage therapy strategies for biofilms, and the quality and safety of phage preparations. However, much consideration is to be taken in designing a novel therapeutic approach for antibiotic-resistant infections by using phages, phage lytic proteins, bioengineered phages, or antibiotics in combination.

Background Uttarakhand is a small state in northern India that comprises mixed population with people dwelling in both hilly and plain areas. Globally, diabetes mellitus (DM) has already been considered to be a pandemic. Furthermore, cardiovascular diseases (CVD) significantly increase mortality and morbidity in patients suffering from DM. Additionally, dyslipidemia has been identified as an important marker in the development of atherosclerosis and ultimately CVD in patients of prediabetes and diabetes. Thus, the identification of subjects with dyslipidemia in prediabetes might be fruitful in lowering their progression to diabetes and ultimately in decreasing incidences of CVD. Hence, this study was undertaken to assess dyslipidemia via the calculation of atherogenic indices (AI) and lipid ratios in prediabetic and diabetic groups attending tertiary care hospital in Uttarakhand. Materials and Methods This study reviewed retrospective biochemical data of 500 study subjects from e-hospital software of the All India Institute of Medical Sciences, Rishikesh. All study subjects were divided into three groups: 122 controls, 137 prediabetics, and 241 diabetics based on the American Diabetes Association criteria. Study subjects were evaluated for glycated hemoglobin (HbA1c), lipid profile, and AI (total cholesterol [TC]/high-density lipoprotein cholesterol [HDLc], low-density lipoprotein cholesterol [LDLc]/HDLc, TC-HDLc/HDLc, triglycerides [TG]/HDLc). Results Results showed that TC, TG, LDLc, and AI were significantly higher, and HDLc was significantly decreased in prediabetic and diabetic groups compared with controls. Furthermore, HbA1c showed significant positive correlation with lipid profile and AI except atherogenic coefficient (TC-HDL/HDL). Conclusion In conclusion, the current study showed the presence of dyslipidemia in both prediabetic and diabetic groups underlining their importance for screening at the prediabetic stage. Hence, we also recommend screening of the prediabetic group for dyslipidemia to arrest the development of early cardiovascular complications. Data were retrieved from electronic laboratory records, so no informed consent form was required in this study. ^# These authors contributed equally and retain the first authorship. Article published online: 09 September 2022 © 2022. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Background & objectives: Gallbladder cancer (GBC) has a low overall survival rate due to late detection and poor prognosis. Chronic inflammation contributes to malignant conversion and metastasis in GBC. Expression of inflammatory proteins, such as signal transducer and activator of transcription factor (STAT) and nuclear factor kappa B (NFĸB) proteins, for diagnosis through immunohistochemistry (IHC) is a promising area of research; however, diagnosis of GBC through IHC-based methods is still in its infancy. So, the present pilot study explores the use of STAT proteins (STAT 3 and 6) and NFĸB as diagnostic biomarkers for GBC. Methods: Histologically confirmed cases of GBC (n=13) and cholelithiasis (n=23) as controls, were recruited. IHC was performed for protein expression of STAT3, STAT6, and NFĸB. Subgrouping into high and low expression was performed based on the receiver operating curve (ROC) analysis. Diagnostic utility and its association with the aggressiveness of cancer were assessed. Results: The mean age of GBC and cholelithiasis patients was 50.84±14.5 and 44.0±11.9 years, respectively. Liver infiltration and metastasis were observed in 61 per cent and 69 per cent of the patients, respectively. STAT3, STAT6, and NFĸB expressions were significantly higher in GBC as compared to cholelithiasis. Sensitivity and specificity for STAT3 and STAT6 were 91, 47 and 75, 39 per cent, respectively. STAT6 expression was associated with lymph node involvement. Whereas, both STAT3 and STAT6 expressions were associated with Liver infiltration. Interpretation & conclusions: This pilot study demonstrated STAT3 and STAT6 as sensitive and specific molecular biomarkers for diagnosing and assessing the aggressiveness of GBC. These may be used as an adjunct to the diagnosis of GBC after validation on a larger sample size.