Journal of Physiology and Biochemistry

Obesity constitutes a global health epidemic which worsens the main leading death causes such as type 2 diabetes, cardiovascular diseases, and cancer. Changes in the metabolism in patients with obesity frequently lead to insulin resistance, along with hyperglycemia, dyslipidemia and low-grade inflammation, favoring a more aggressive tumor microenvironment. One of the hallmarks of cancer is the reprogramming of the energy metabolism, in which tumor cells change oxidative phosphorylation to aerobic glycolysis or "Warburg effect"...

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Exosomes are small extracellular vesicles secreted by almost all cell types, and carry diverse cargo including RNA, and other substances. Recent studies have focused exosomal microRNAs (miRNAs) on various human diseases, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (METS) which accompany the occurrence of insulin resistance. The regulation of insulin signaling has connected with some miRNA expression which play a significant regulatory character in insulin targeted cells or organs, such as fat, muscle, and liver...

Recent progresses in diagnostic and therapeutic methods have significantly improved prognosis in cancer patients. However, cancer is still considered as one of the main causes of human deaths in the world. Late diagnosis in advanced tumor stages can reduce the effectiveness of treatment methods and increase mortality rate of cancer patients. Therefore, investigating the molecular mechanisms of tumor progression can help to introduce the early diagnostic markers in these patients. MicroRNA (miRNAs) has an important role in regulation of pathophysiological cellular processes...

Extracellular vesicles (EVs) are involved in both physiological and pathological processes in many organ systems and are essential in mediating intercellular communication and maintaining organismal homeostasis. It is helpful to propose new strategies for disease treatment by elucidating the mechanisms of EV release and sorting. An increasing number of studies have shown that there is specific homeostasis in EVs, which is helpful for the human body to carry out physiological activities. In contrast, an EV homeostasis im-balance promotes or accelerates disease onset and development...

MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that regulate gene expression at the post-transcriptional level. A cross-kingdom regulatory function has been unveiled for plant miRNAs (xenomiRs), which could shape inter-species interactions of plants with other organisms (bacteria and humans) and thus, be key functional molecules of plant-based food in mammals. However, discrepancies regarding the stability and bioavailability of dietary plant miRNAs on the host cast in doubt whether these molecules could have a significant impact on human physiology...

Ovalbumin (OVA) is a major allergen in eggs and could induce severe allergic reactions in sensitive individuals, where the innate immune system works as a regulator. The mechanism of how innate immunity adjusts to food allergy is relatively well-studied, however, the effects of allergen uptake on the innate immune system remain unclear. Therefore, the Caenorhabditis elegans (C. elegans) model was utilized to assess the effects of OVA on its innate immune system. OVA enhanced the immune response of C. elegans with higher survival rates under Pseudomonas aeruginosa infection...

Fasting and fasting-mimicking conditions modulate tumor metabolism and remodel the tumor microenvironment (TME), which could be exploited for the treatment of tumors. A body of evidence demonstrates that fasting and fasting-mimicking conditions can kill cancer cells, or sensitize them to the antitumor activity of standard-of-care drugs while protecting normal cells against their toxic side effects. Pre- and clinical data also suggest that immune responses are involved in these therapeutic effects. Therefore, there is increasing interest in evaluating the impact of fasting-like conditions in the efficacy of antitumor therapies based on the restoration or activation of antitumor immune responses...

The physical and functional interaction between transient receptor potential channel ankyrin 1 (TRPA1) and neuronal calcium sensor 1 (NCS-1) was assessed. NCS-1 is a calcium (Ca2+ ) sensor found in many tissues, primarily neurons, and TRPA1 is a Ca2+ channel involved not only in thermal and pain sensation but also in conditions such as cancer and chemotherapy-induced peripheral neuropathy, in which NCS-1 is also a regulatory component.We explored the interactions between these two proteins by employing western blot, qRT-PCR, co-immunoprecipitation, Ca2+ transient monitoring with Fura-2 spectrophotometry, and electrophysiology assays in breast cancer cells (MDA-MB-231) with different levels of NCS-1 expression and neuroblastoma cells (SH-SY5Y)...

Hepatocellular carcinoma (HCC) is a highly vascularized tumor, one of the most common and lethal cancer-related tumor deaths worldwide, with cell proliferation playing a key role. In this study our western blot results and data from TAGC demonstrate a strong association between Sorcin (SRI) overexpression and poor outcomes in HCC. Moreover, SRI overexpression was remarkably effective in promoting proliferation in vitro and increasing tumor growth in vivo, which were attenuated by knocking down SRI. Mechanistically, SRI regulated vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor B (VEGFB) through PI3K/Akt/FOXO1 signal pathway...

Hypothermia is an essential environmental factor in gastrointestinal diseases, but the main molecular mechanisms of pathogenesis remain unclear. The current study sought to better understand how chronic cold stress affects gut damage and its underlying mechanisms. In this work, to establish chronic cold stress (CS)-induced intestinal injury model, mice were subjected to continuous cold exposure (4 °C) for 3 h per day for 3 weeks. Our results indicated that CS led to gut injury via inducing changes of heat shock proteins 70 (HSP70) and apoptosis-related (caspases-3, Bax and Bcl-2) proteins; enhancing expression of intestinal tight-related (ZO-1 and occludin) proteins; promoting releases of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), high mobility group box 1 (HMGB1), interleukin1β (IL-1β), IL-18 and IL-6 inflammatory mediators in the ileum; and altering gut microbial diversity...

In eukaryotes such as humans, some non-coding single-stranded RNAs (ncRNAs) help to regulate the pre- and post-transcriptional expression of certain genes, which in turn control many important physiological processes, such as cell proliferation, distinctions, invasion, angiogenesis, and embryonic development. microRNA-126 is an important member of these miRNAs that can be directly or indirectly involved in the control of angiogenesis. Recently, numerous studies have expounded that microRNA-126 can inhibit or promote angiogenesis as well as attenuate inflammatory responses through complex molecular mechanisms...

The endoplasmic reticulum (ER) is determinant to maintain cellular proteostasis. Upon unresolved ER stress, this organelle activates the unfolded protein response (UPR). Sustained UPR activates is known to occur in inflammatory processes, deeming the ER a potential molecular target for the treatment of inflammation. This work characterizes the inflammatory/UPR-related molecular machinery modulated by an in-house library of natural products, aiming to pave the way for the development of new selective drugs that act upon the ER to counter inflammation-related chronic diseases...

Current study investigated the impact of maternal and postnatal overnutrition on phenotype of adipose, in relation to offspring thermogenesis and sex. Female C57BL/6 J mice were fed with CHOW or high fat diet (HFD) for 2 weeks before mating, throughout gestation and lactation. At weaning, pups were fed to 9 weeks old with CHOW or HFD, which resulted in four groups for each gender--male or female: CHOW-CHOW (CC), CHOW-HFD (CH), HFD-CHOW (HC), HFD-HFD (HH). Maternal and post-weaning HFD enhanced thermogenic factors such as Acox1, Dio2 and Cox8b in iBAT of male and female offspring, but increased SIRT1, PGC-1α and UCP1 only in female...

Hepatocellular carcinoma (HCC) is one of the most aggressive and dismal cancers globally. Emerging evidence has established that mTOR and Hippo pathways are oncogenic drivers of HCC. However, the prognostic value of these pathways in HCC remains unclear. In this study, we aimed to develop a gene signature utilizing the mTOR/Hippo genes for HCC prognostication. A multiple stage strategy was employed to screen, and a 12-gene signature based on mTOR/Hippo pathways was constructed to predict the prognosis of HCC patients...

Corticosterone (CORT) damages hippocampal neurons as well as induces neuroinflammation. The tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis is a form of programmed cell death, also known as inflammatory cell death. Menin is a multifunctional scaffold protein, which deficiency aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation as well as necroptosis and further investigated the mediatory role of Menin in this protective effect of itaconate by using an exposure of CORT to HT22 cells (a hippocampal neuronal cell line)...

The insulin receptor (IR) plays an important role in insulin signal transduction, the defect of which is believed to be the root cause of type 2 diabetes. In 3T3-L1 adipocytes as in other cell types, the mature IR is a heterotetrameric cell surface glycoprotein composed of two α subunits and two β subunits. Our objective in our study, is to understand how the desialylation of N-glycan chains, induced by elastin-derived peptides, plays a major role in the function of the IR. Using the 3T3-L1 adipocyte line, we show that removal of the sialic acid from N-glycan chains (N893 and N908), induced by the elastin receptor complex (ERC) and elastin derived-peptides (EDPs), leads to a decrease in the autophosphorylation activity of the insulin receptor...

Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of skeletal muscle regeneration dysfunction. This study aimed to examine the effects and mechanisms of lactate (Lac) treatment on PA-induced impairment of C2C12 cell differentiation capacity. Furthermore, the involvement of voltage-gated calcium channels in this context was examined. In this study, Lac could improve the PA-induced impairment of differentiative capacity in C2C12 cells by affecting Myf5, MyoD and MyoG...

Inositol-requiring enzyme-1 (IRE1) is the master regulator of the unfolded protein response pathway, associated with the endoplasmic reticulum (ER) in sensing and regulating cell stress. The activity of IRE1 is highly explored and well-characterized in cancer and other cells. However, the IRE1 molecular mechanism in chondrocytes is poorly understood. The present study explored the effect of IRE1 on chondrocytes regarding its chondrogenic gene expression and its correlation with different cellular pathways and cell behavior...

Pyruvate kinase M2 (PKM2), a subtype of pyruvate kinase (PK), has been shown to play an important role in the development of cancer. It regulates the last step of glycolytic pathway. PKM2 has both pyruvate kinase and protein kinase activity, and the conversion of these two functions of PKM2 depends on the mutual change of dimer and tetramer. The dimerization of PKM2 can promote the proliferation and growth of tumor cells, so inhibiting the dimerization of PKM2 is essential to curing cancer. The aggregation of PKM2 is regulated by both endogenous and exogenous cofactors as well as post-translational modification (PTM)...