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Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration. [ABSTRACT FROM AUTHOR]

The C-C motif chemokine ligand-2 (CCL2) was evidenced to be associated with tuberculosis susceptibility in some ethnic groups. In the present study, effort was made to find out the association of CCL2-2518 A>G and -362 G>C variants with susceptibility to TB in a population from North India. The genotyping was carried out in 373 participants with pulmonary TB (PTB) and 248 healthy controls (HCs) for CCL2-2518 A>G and -362 G>C polymorphisms by PCR-RFLP and by melting curve analysis using fluorescence-labeled hybridization fluorescent resonance energy transfer (FRET) probes, respectively, followed by DNA sequencing in a few representative samples. Genotype and allele frequencies were compared by the chi-squared test and crude and Mantel-Haenszel (M-H) odds ratio (OR). OR was calculated using STATA/MP16.1 software. Further, CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β levels were measured in serum samples of these participants using commercially available kits. Our analysis indicated that the homozygous mutant in both -2518 GG (OR = 2.07, p = 0.02) and -362 CC (OR = 1.92, p = 0.03) genotypes was associated with susceptibility to pulmonary TB. Further, heterozygous genotypes -2518AG (OR = 0.60, p = 0.003) and -362GC (OR = 0.64, p = 0.013) provide resistance from PTB disease. Haplotype analysis revealed AC haplotype (p = 0.006) to be a risk factor associated with PTB susceptibility. The serum CCL2 level was significantly elevated among participants with -2518 AA genotype compared to -2518 GG genotype. CCL2 level was observed to be positively correlated with IL12p70, IFN-γ and TNF-α, thus suggesting the immunological regulatory role of CCL2 against pulmonary tuberculosis. CCL2-2518 GG and -362 CC genotypes were found to be associated with susceptibility to pulmonary tuberculosis and CCL2-2518AG and CCL2-362GC with resistance from PTB. AC haplotype was found to be a risk factor for PTB in the present study. It may be hypothesized from the findings that -2518G allele could be responsible for lower production of CCL2 which leads to defective Th1 response and makes a host susceptible for pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

The allelic family of HLA‐A*02 with a repertoire of approximately 1022 alleles represents the predominant and most heterogeneous group at the HLA‐A locus. This remarkable diversity signifies its evolutionary relevance. Its population‐specific diversity is attributed to environmental factors and pathogen pressure and can be harnessed in biology and medicine, particularly in disease association and for HLA‐based vaccination approaches. We therefore investigated the HLA‐A*02 repertoire in two North Indian caste populations, viz Punjabi Khatries (PK, N = 250), Kashmiri Brahmins (KB, N = 160) and a Central Indian tribe Sahariya (ST, N = 100) using Luminex‐based high‐resolution rSSO method. When required, results were confirmed with high‐resolution PCR‐SSP and/or next‐generation sequencing (NGS). In the three populations evaluated, HLA‐A*02 was observed with an overall high phenotypic/allelic frequency, however, A*02 repertoire differed among them. A total of six alleles were observed (A*02:01, *02:03, *02:05, *02:06, *02:07 and *02:11) in the caste groups, compared with four (except *02:05 and *02:07) in the tribals. Our striking observation was the high occurrence of A*02:11 at the repertoire level (80.6% in ST, 39% in PK, 31.8% in KB). Globally, this allele is rare, observed with low frequencies in limited ethnic groups. The primordial A*02:01 allele, representative A*02 allele in most ethnicities was observed as the second predominant allele (PK = 27.3%, KB = 31.8% and ST = 11.9%). Extremely high occurrence of A*02:11 in ST may be representation of ancient Austro‐Asiatic genetic pool. In caste populations, the observed A*02 repertoire may be a consequence of natural selection and/or admixture from different populations. [ABSTRACT FROM AUTHOR]

Hsp27, a highly conserved small molecular weight heat shock protein, is widely known to be developmentally regulated and heat inducible. Its role in thermotolerance is also implicated. This study is a sequel of our earlier studies to understand the molecular organization of heat shock genes/proteins and their role in development and thermal adaptation in a sheep pest, Lucilia cuprina (blowfly), which exhibits unusually high adaptability to a variety of environmental stresses, including heat and chemicals. In this report our aim was to understand the evolutionary relationship of Lucilia hsp27 gene/protein with those of other species and its role in thermal adaptation. We sequence characterized the Lchsp27 gene (coding region) and analyzed its expression in various larval and adult tissues under normal as well as heat shock conditions. The nucleotide sequence analysis of 678 bps long-coding region of Lchsp27 exhibited closest evolutionary proximity with Drosophila (90.09%), which belongs to the same order, Diptera. Heat shock caused significant enhancement in the expression of Lchsp27 gene in all the larval and adult tissues examined, however, in a tissue specific manner. Significantly, in Malpighian tubules, while the heat-induced level of hsp27 transcript (mRNA) appeared increased as compared to control, the protein level remained unaltered and nuclear localized. We infer that Lchsp27 may have significant role in the maintenance of cellular homeostasis, particularly, during summer months, when the fly remains exposed to high heat in its natural habitat. [ABSTRACT FROM AUTHOR]

Background: Poor prognosis in gallbladder cancer is due to late presentation of the disease, lack of reliable biomarkers for early diagnosis and limited targeted therapies. Early diagnostic markers and novel therapeutic targets can significantly improve clinical management of gallbladder cancer.Methods: Proteomic analysis of four gallbladder cancer cell lines based on the invasive property (non-invasive to highly invasive) was carried out using the isobaric tags for relative and absolute quantitation labeling-based quantitative proteomic approach. The expression of macrophage migration inhibitory factor was analysed in gallbladder adenocarcinoma tissues using immunohistochemistry. In vitro cellular assays were carried out in a panel of gallbladder cancer cell lines using MIF inhibitors, ISO-1 and 4-IPP or its specific siRNA.Results: The quantitative proteomic experiment led to the identification of 3,653 proteins, among which 654 were found to be overexpressed and 387 were downregulated in the invasive cell lines (OCUG-1, NOZ and GB-d1) compared to the non-invasive cell line, TGBC24TKB. Among these, macrophage migration inhibitory factor (MIF) was observed to be highly overexpressed in two of the invasive cell lines. MIF is a pleiotropic proinflammatory cytokine that plays a causative role in multiple diseases, including cancer. MIF has been reported to play a central role in tumor cell proliferation and invasion in several cancers. Immunohistochemical labeling of tumor tissue microarrays for MIF expression revealed that it was overexpressed in 21 of 29 gallbladder adenocarcinoma cases. Silencing/inhibition of MIF using siRNA and/or MIF antagonists resulted in a significant decrease in cell viability, colony forming ability and invasive property of the gallbladder cancer cells.Conclusions: Our findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for gallbladder cancer. [ABSTRACT FROM AUTHOR]

Background: Patients presenting with mass lesions of liver and gallbladder are a common occurrence in a cancer hospital in north central part of India. Fine-needle aspiration cytology (FNAC) serves as first line of pathological investigations, but there are pros and cons involved. Aim: The main objective of the present study was to establish adequacy of the procedure and to find out diagnostic pitfalls. An attempt was made to analyze inconclusive and inadequate aspirations. Materials and Methods: A total of 400 consecutive fine-needle aspirates of liver, belonging to 328 cases over a period of 2 years, were analyzed. Hematoxylin and eosin and May-Grünwald-Giemsa stains were used. Chi-square test was carried out to compare significant degree of difference in different kind of diagnosis. Results: Out of 400 aspirations, 289 (72.2%) were adequate, 75 (18.7%), inconclusive and 36 (9%), inadequate. Among positive aspirations the most common was metastatic adenocarcinoma, 128 (44.2%). The positive diagnosis and adequate aspirations were significantly high (P < 0.0001). Major differential diagnostic problems were: Distinguishing the poorly differentiated hepatocellular carcinoma from the metastatic adenocarcinoma; and leukemia/lymphoma from other malignant round cell tumors. Common diagnostic pitfalls were repeated aspirations from the necrotic area and aspiration of atypical, disorganized and reactive hepatocytes, adjacent to a metastasis. No complications were observed. Conclusion: FNAC can be used successfully for the diagnosis of liver and gallbladder lesions, thus avoiding open biopsy. Study indicates the potential of using FNAC in clinical intervention where the incidence of gall-bladder and liver cancer is very high and open biopsy and surgery are not an option. [ABSTRACT FROM AUTHOR]

Highlights: [•] Quantitative proteomic analysis of gallbladder cancer. [•] LC–MS/MS analysis using Fourier transform high resolution mass spectrometry. [•] 2575 proteins identified including several upregulated lysosomal proteins. [•] Prosaposin and transgelin validated as candidate markers using tissue microarrays. [Copyright &y& Elsevier]