Cell Biochemistry and Biophysics最新文献

In the regulation of gene expression, epigenetic factors, including non-coding RNAs (ncRNAs) play a role in genetics. Among the ncRNA family, microRNAs (miRNAs) have gained significant attention for their involvement in post-transcriptional gene regulation, with profound implications for both normal and pathological processes including neurological diseases such as hypoxic-ischemic brain injury. A specific miRNA, called miR-122-5p, has gained attention in hypoxic-ischemic conditions, where it modulates critical pathways such as inflammation, oxidative stress, and neuronal survival. The purpose of this review is to highlight recent advances in the biogenesis, expression, and regulation of miR-122-5p, focusing on its role in hypoxic-ischemic conditions and its potential as a therapeutic target. We first studied the therapeutic strategies and potential clinical applications of miR-122-5p, our research showing it interacts with key transcription factors, such as HIF-1α and NF-κB, influencing cellular responses to low oxygen levels. Our findings revealed that miR-122-5p plays a vital role in hypoxic-ischemic brain injury, with its abnormal levels strongly associated with increased brain damage and neuroinflammation, suggesting its potential as a promising therapeutic target. Furthermore, miR-122-5p influences various biological processes in the brain, such as metabolism and blood vessel formation. The use of miR-122-5p inhibitor has been shown to increase autophagy, reduce apoptosis, and decrease oxidative stress and inflammation, thereby protecting neurons and improving outcomes in hypoxic encephalopathy by targeting multiple genes related to these processes. Conversely, miR-122-5p mimics exacerbate oxidative stress and reduce autophagy. These findings highlight the therapeutic potential of miR-122-5p inhibition in reducing brain injury and promoting recovery in hypoxic-ischemic encephalopathy through enhanced neuroprotective mechanisms and the suppression of harmful cellular processes. However, further experimental studies are needed to fully understand the therapeutic potential of targeting miR-122-5p and its related genes in hypoxic-ischemic encephalopathy.

Specific myogenic microRNAs termed "myomiRNAs" are involved in skeletal muscle development and regeneration, and an obesogenic environment in utero may affect these processes. The present study aimed to determine whether this environment induced variations in the expression levels of myomiRs-31, -133, -136, -206, and -296 and whether the administration of (-)-epicatechin (Epi), an exercise mimetic, could modify these variations. Rat Wistar male offspring from control mothers (C) or obese mothers (MO) were treated (C+Epi and MO+Epi) or not treated with Epi (C and MO). MyomiRNA expression in the gastrocnemius and soleus muscles was analyzed via RT‒qPCR, and bioinformatic analysis was used to predict the participation of these miRNAs in different skeletal muscle signal transduction pathways. The expression of myomiRNA-31-5p in the gastrocnemius and soleus was significantly lower in the Epi-treated groups (C+Epi and MO+Epi vs. C and MO). The expression of myomiRNA-206 increased in the gastrocnemius muscles of the MO and MO+Epi groups but decreased in the soleus muscles of the MO and MO+Epi groups. The expression of myomiRNA-296 was increased in the MO group in the gastrocnemius and soleus but was reduced in the Epi stimulus group. The expression of myomiRNA-486 increased in the gastrocnemius of the C+Epi group and decreased in the soleus of the MO+Epi group (p = 0.028 vs. MO). In conclusion, we show that an intrauterine obesogenic environment differentially affects the expression levels of some myomiRNAs and that this effect is modified by epicatechin.

The development of innovative, eco-friendly methods for synthesizing functional nanoparticles is crucial in advancing cancer therapeutics. This study highlights a one-pot in situ synthesis of paclitaxel-functionalized gold nanoparticles (PTX-AuNPs), with paclitaxel serving as both the reducing and stabilizing agent. The synthesis process was validated using UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and high-resolution transmission electron microscopy (FEG-TEM). High-performance liquid chromatography (HPLC) confirmed the purity and structural integrity of paclitaxel before and after synthesis. The resulting PTX-AuNPs exhibited potent anticancer activity against human cervical cancer (SiHa) and human colon cancer (HT-29) cell lines, with a significantly stronger effect on the HT-29 cell line. A concentration-dependent reduction in HT-29 cell growth was observed as nanoparticle concentrations increased from 10 µg/mL-20 µg/mL. Molecular docking studies further demonstrated paclitaxel's strong binding affinity (-8.5 kcal/mol) to β-Tubulin, elucidating its anticancer mechanism. This cost-effective and environmentally friendly approach offers significant promise for enhancing cancer treatment strategies.

Metformin, a biguanide drug, is used for its antihyperglycemic effects. The purpose of the present study was to investigate the effects of metformin on the experimental model of intestinal ischemia-reperfusion (I/R) injury. Ischemia was induced by superior mesenteric artery occlusion followed by reperfusion. Metformin was administered orally by gavage at doses of 50, 100 or 200 mg/kg for one week before the surgery. Rats were divided to five groups (n = 8 for each): Sham control group; I/R control group; Metformin50 treated I/R group; Metformin100 treated I/R group; and Metformin200 treated I/R group. Tissue levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1), toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) as well as histological analysis were evaluated. Metformin treatment decreased the levels of MDA in 100 and 200 mg/kg doses besides lowering the MPO activity and ICAM-1 levels in all doses. Metformin also reduced NF-κB levels at dose of 200 mg/kg and improved histopathological scores at doses of 100 and 200 mg/kg. The treatment with metformin can prevent I/R-induced intestinal injury through down-regulating ICAM-1 and NF-κB levels, reducing oxidative stress, and lowering neutrophil accumulation. We propose that metformin could be a therapeutic agent in intestinal I/R.

This study aimed to investigate how bromelain protects glial cells from pentylenetetrazole (PTZ)-induced damage, focusing on its anti-inflammatory effects. C6 glioma cells were treated with PTZ, bromelain, or a combination of PTZ and bromelain. The interactions of bromelain with iNOS (Inducible Nitric Oxide Synthase) and COX2 (Cyclooxygenase-2) were investigated using molecular docking calculations. Cell viability was measured using the XTT (Methoxynitrosulfophenyl-Tetrazolium Carboxanilide) assay. iNOS, NO (Nitric Oxide), and COX2 levels were assessed using ELISA and immunofluorescence staining. Bromelain at 50 and 100 µg/mL significantly increased cell viability (p < 0.001). On the other hand, bromelain at 50 µg/mL reduced inflammation, as indicated by lower levels of NO, iNOS, and COX2 (p < 0.001). In-silico predictions suggest that bromelain can effectively target iNOS and COX2, key inflammatory proteins. These findings indicate that bromelain protects glial cells by exerting anti-inflammatory effects. However, further research is needed to understand the underlying mechanisms fully.

Acute liver injury (ALI) is a vital factor in the early progression of severe acute pancreatitis (SAP). It exacerbates systemic inflammation, impairs the liver's capacity to clear inflammatory mediators and cytokines, and contributes to systemic organ dysfunction syndrome (SODS). However, the mechanisms driving SAP-associated liver injury (SAP-ALI) are poorly understood, and effective therapeutic options remain limited. Chaperone-mediated autophagy (CMA), a selective form of autophagy, plays an essential role in reducing inflammation and oxidative stress by clearing damaged or dysfunctional proteins. This study examines the role of CMA in SAP-ALI and evaluates its therapeutic potential. In a sodium taurocholate-induced SAP-ALI rat model, CMA dysfunction was observed, characterized by reduced LAMP2A expression and the accumulation of CMA substrate proteins in pancreatic and hepatic tissues. The activator AR7 successfully restored CMA function, enhanced anti-inflammatory and antioxidant responses, and mitigated pancreatic and liver damage in SAP rat. In contrast, the CMA inhibitor PPD exacerbated liver injury, underscoring CMA's protective role in SAP-ALI. Mechanistic analyses demonstrated that CMA reactivation activated the Keap1/Nrf2 signaling pathway, leading to increased expression of antioxidant-related genes and suppression of NLRP3 inflammasome activation. Specifically, the protective effects of AR7-induced CMA activation were significantly reversed by the Nrf2 inhibitor ML385, which inhibited Nrf2 signaling and its associated protein levels. These findings show AR7-induced CMA reactivation as a promising therapeutic strategy for SAP-ALI, primarily through its enhancement of Keap1/Nrf2-regulated antioxidant pathways and inhibition of NLRP3 inflammasome activation.

Chronic kidney disease (CKD) is a clinical syndrome of metabolic disorder caused by progressive kidney impairment for more than 3 months. CKD has become a global public health problem due to its high morbidity and mortality, which is difficult to be cured for most patients. The pathogenesis of CKD is still unclear, which is closely related to glomerulosclerosis, kidney tubular injury and kidney fibrosis. LncRNA is a non-coding RNA with a length of more than 200 nucleotides. It not only participates in intracellular transcriptional regulation, post-transcriptional regulation and epigenetic activities, but also forms a regulatory network together with miRNA and mRNA, to further conduct the reticular regulation in cells. Recently, it has been found that lncRNA participates in pathophysiological mechanism of CKD by regulating glomerulosclerosis, kidney tubular injury and kidney fibrosis. This has also become a new direction of lncRNA in early diagnosis and targeted therapy of CKD.

Lipopolysaccharide (LPS)-induced inflammatory liver injury can cause significant tissue damage and apoptosis. Homeopathic formulations such as Tarantula cubensis venom show potential in regulating inflammation. This study's objective was to assess theranecron's (THE) impact on inflammation and oxidative stress in a model of liver injury caused by lipopolysaccharide (LPS). Wistar albino female rats were used in this investigation, and they were split up into four groups of eight each: Control, LPS, LPS+THE, and THE. Single-dose treatments were administered to the respective groups on the same day. Liver tissues were collected 6 h after LPS treatment for histopathological, immunohistochemical, biochemical, and genetic evaluations. Total antioxidant status (TAS) was lower, total oxidant status (TOS) and oxidative stress index (OSI) were higher, and the LPS group had higher levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and macrophage antigen-1 (CD11B). Significant liver damage was also seen in this group, as evidenced by elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and decreased albumin. Nuclear factor erythroid 2-related factor 2 (Nrf2), Sirtuin 1 (SIRT1), heme oxygenase 1 (HO-1), kelch-like ECH-associated protein 1 (Keap1), and glutathione peroxidase 4 (GPx4) were all found to be downregulated by gene expression analysis. However, THE therapy was shown to reverse all of these findings in the LPS+THE group. The THE group similarly maintained baseline levels of these markers and showed no adverse effects. In conclusion, Theranekron showed hepatoprotective effects in LPS-induced liver injury by reducing oxidative stress and inflammation and regulating antioxidant gene expression, possibly through IL-6 and TNF-α.

Despite significant efforts in recent years to clean up the environment, pollution remains a major issue. Bioremediation is the most effective and ecologically friendly way to clean and regenerate chemically polluted environments. Microorganisms' biostabilization of soluble and insoluble forms of hazardous contaminants can be employed to remediate areas contaminated with heavy metals. Understanding how contaminants affect and disrupt intracellular structures and functions is a prerequisite to using microorganisms. The study focuses on the exposure of soil bacteria A. oxydans to Cu (II) and Cs (I). The stability of subcellular structures and intracellular processes leading to cell death or adaptation were assessed using the Differential Scanning Calorimetry (DSC) method. The DSC could lay out in sequence the complex series of denaturation events that take place when cells are heated. The DSC analysis provided the possibility to verify the character of the studied metal action at the whole bacteria cell level at the early stage of metal action.

Endometrial cancer is a prevalent type of cancer among women worldwide. The irregularity of the PI3K/AKT/mTOR signaling pathway plays a role in the pathogenesis of many cancer types. MicroRNAs are small noncoding RNAs that play crucial roles in the pathogenesis of different cancer types. MicroRNAs target many key components of the PI3K/AKT/mTOR pathway in human tumors. In this study the PI3K/AKT/mTOR pathway was affected in endometrial cancer, and the expression levels of miR-7, miR-17, miR-145, miR-155, miR-206, miR-221, miR-222 were determined. In addition, in silico analyses were examine the molecular interactions between miRNAs and target genes. Identifying dysregulated miRNA expression in endometrial cancer is important for developing miRNA-based therapeutic strategies. In our study, Grade 1 (n = 16), Grade 2 (n = 16), Grade 3 (n = 16), tissues diagnosed with endometrioid adeno carcinoma, control 1 (n = 16) secretory phase and control 2 (n = 16) proliferative phase healthy endometrial tissues without endometrial cancer were included. miRNA expression analysis was performed using the real-time PCR. In our study, the expression of miR-7-5p, miR-145-5p, and miR-206 decreased, whereas the expression of miR-17-5p, miR-221-3p, and miR-222-3p increased in endometrial cancer (p < 0,05). Statistically significant results were not obtained to for the expression levels of miR-21-5p and miR-155-5p. miR-7-5p targets PIK3CD, PIK3R3, PIK3CB and AKT3, miR-17-5p targets PIK3R1 and AKT3, miR-21-5p target PIK3R1, miR-145-5p target AKT3, miR-155-5p targets PIK3CA and PIK3R1, miR-206 target PIK3C2A, miR-221-3p and miR-222-3p target PIK3R1 as identified via in silico analysis. These results can shed light on the development of molecular-targeted therapy strategies. Treatment strategies can be developed by designing ASOs, LNAs, miRNA antagomirs, or miRNA sponges for upregulated miR-17-5p, miR-221-3p, and miR-222-3p, and miRNA mimics for downregulated miR-7-5p, miR-145-5p, and miR-206.