Molecular Biology Reports最新文献

Background: Exposure to ionizing radiation is inevitable due to its extensive use in industrial and medical applications. The search for effective and safe natural therapeutic agents as alternatives to chemical drugs is crucial to mitigate their side effects. This study aimed to evaluate the effects of citicoline as a standalone treatment or in combination with the anti-hepatotoxic drug silymarin in protecting against liver injury caused by γ-radiation in rats.

Methods and results: The rats were exposed to γ-radiation (7 Gy) and treated with citicoline (300 mg/kg/day) and/or silymarin (50 mg/kg/day). The results showed that citicoline alleviated liver damage in irradiated rats by reducing hepatic malondialdehyde levels, serum aspartate aminotransferase activity, and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). It also increased acetylcholine (ACh) levels and the gene expression of the anti-inflammatory protein α7 nicotinic acetylcholine receptor (α7nAChR). Additionally, citicoline improved serum triiodothyronine (T3) levels, thyroid hormone receptor beta (TRβ) gene expression, and iodothyronine deiodinase type 1 activity in hepatic tissues of irradiated rats. Furthermore, citicoline enhanced the effects of silymarin on thyroxine (T4), TRβ, ACh, and α7nAChR when co-administered in irradiated rats. Histopathological analysis confirmed these findings, demonstrating improved liver tissue structure.

Conclusions: Citicoline mitigates γ-radiation-induced liver damage by reducing oxidative stress, activating the cholinergic anti-inflammatory pathway, and modulating thyroid hormone metabolism. These findings support the use of citicoline as a safe standalone treatment or as an adjuvant with silymarin for managing liver damage and thyroid hormone disturbances caused by γ-irradiation.

Background: von Hippel-Lindau (VHL) hereditary cancer syndrome is caused by mutations in the VHL tumor suppressor gene and is characterized by a predisposition to form various types of tumors, including renal cell carcinomas, hemangioblastomas, and pheochromocytomas. The protein products of the VHL gene, pVHL, are part of an ubiquitin ligase complex that tags hypoxia inducible factor alpha (HIF-α) for proteosomal degradation. pVHL has also been reported to bind to atypical protein kinase C (aPKC).

Methods and results: To better understand the relationship between pVHL and aPKC, the PKC iota (PKCι) isoform of aPKC was knocked out in renal carcinoma cells, both pVHL-negative and those with replaced pVHL. Cellular properties associated with pVHL function were assayed. Knockout of PKCι in pVHL-expressing cells led to greater downregulation of HIF-α than seen with pVHL alone, suggesting that the presence of PKCι opposes complete regulation of HIF-α by pVHL. In contrast, absence of either pVHL or PKCι disrupted tight junction formation and led to upregulated levels of α5 integrin, both of which were phenocopied by lysosomal inhibition. LAMP1 (lysosome associated membrane protein 1), a marker for lysosomes, showed dysregulated localization and altered electrophoretic gel migration in the absence of pVHL. While the upregulated α5 integrin seen in the absence of either pVHL or PKCι loss was associated with increased cell adhesion, loss of pVHL caused increased cell motility whereas loss of PKCι decreased motility.

Conclusions: These data are consistent with a known role of PKCι in endocytosis of α5 integrin and suggest a subsequent novel role of pVHL in targeting a pool of endocytosed α5 integrin for lysosomal degradation.

Background: Pseudomonas aeruginosa's inherent and adapted resistance makes this pathogen a serious problem for antimicrobial treatments. Furthermore, its biofilm formation ability is the most critical armor against antimicrobial therapy, and the virulence factors, on the other hand, contribute to fatal infection and other recalcitrant phenotypic characteristics. These capabilities are harmonized through cell-cell communication called Quorum Sensing (QS), which results in gene expression regulation via three major interconnected circuits: las, rhl, and pqs system. Pqs circuit specificity in P. aeruginosa made this system an attractive target for antipseudomonal therapy. The current study focuses on novel chalcone derivatives that attenuate P. aeruginosa's pathogenicity by inhibiting the QS system. Chalcones are included in the flavonoid class of phenolic compounds. This family forms one of the greatest groups of bioactive natural products.

Method: The chalcone derivatives's potential activity against the QS system was evaluated through biofilm inhibition, decreased virulence factors production, and gene expression.

Results: Among all the tested compounds, 5H and NMe₂ chalcone derivatives reduced biofilm formation by 60.9% and 78.9%, respectively, and virulence factors production, including pyocyanin (decreased by 5H 30.9% and NMe2 30.7%) and pyoverdine (decreased by 5H 47.1% and NMe2 56.9%) and the QS gene expression (LasR, RhlR, and PqsR) more effectively than other derivatives.

Conclusion: These chalcone compounds can be used as a supplement besides antimicrobial chemotherapy to attenuate pseudomonas pathogenicity.

Background: Breast carcinoma stands out as the most widespread invasive cancer and the top contributor to cancer-related mortality in women. Nanoparticles have emerged as promising tools in cancer detection, diagnosis, and prevention. In this study, the antitumor and apoptotic capability of silver nanoparticles synthesized through Scrophularia striata extract (AgNPs-SSE) was investigated toward breast cancer cells.

Methods: The produced AgNPs-SSE were identified using scanning electron micrograph (SEM), energy-dispersive X-ray (EDAX) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The cell-killing effects of AgNPs-SSE on MDA-MB231 mammary carcinoma cells were evaluated in vitro using the MTT assay over 24 h. Apoptosis induction was conducted by cell cycle analysis, annexin V-FITC/PI staining, reactive oxygen species (ROS) generation, and Hoechst staining. Additionally, the gene expression of βcatenin, GSK3β, and CyclinD1 was analyzed using quantitative real-time PCR (qRT-PCR).

Results: Microscopic analysis confirmed the successful fabrication of globular AgNPs-SSE, with a mean particle dimension of 19 ± 10 nm. The MTT assay revealed that IC₅₀ value of AgNPs-SSE was 48.5 µg/mL for mammary carcinoma cells and 114 µg/mL for normal cells. Annexin V-FITC/PI staining specified that 85.88% of cancer cells treated with AgNPs-SSE underwent either early or late apoptosis. Treatment with AgNPs-SSE also caused a considerable rise in the subG1 cell cycle population and ROS production. Furthermore, the upregulation of βcatenin and downregulation of CyclinD1 gene expression confirmed the apoptotic mechanism.

Conclusions: In conclusion, the findings suggest that phyto-synthesized AgNPs-SSE can restrain the expansion of breast carcinoma cells and provoke apoptosis through oxidative stress. These results highlight the potential of AgNPs-SSE as an antitumor agent against breast cancer.

Background: Acute systemic inflammation affects many organs and it occurs in a wide range of conditions such as acute lung injury (ALI). Inflammation-triggered oxidative pathways together with the caspase activation seen in ALI, result in apoptosis. Dapagliflozin (DPG) is an agent that is known to have oxidative stress-reducing and anti-inflammatory effects in many tissues.

Methods and results: Thirty-two Wistar albino rats were divided into four groups: control, lipopolysaccharide (LPS) (5 mg/kg), LPS + DPG (10 mg/kg) and DPG. DPG was orally administered for five consecutive days LPS was intraperitoneally applied in a single dose on the fifth day and the animals were euthanized six hours after the last drug administration. Lung tissues were harvested. In addition to hematoxylin-eosin staining, caspase-3 (Cas-3) and tumor necrosis factor alpha (TNF-α) immunostainings were conducted. While total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were examined biochemically, Sirtuin-1 (SIRT-1), Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), B-cell lymphoma 2 (Bcl-2), and Bcl-2 associated X protein (Bax) were examined by PCR. Histopathological analysis revealed hyperemia, edema, inflammatory cell infiltration, and epithelial cell loss. In LPS group, Cas-3, TNF-α, TOS, OSI, and Bax values increased whereas SIRT-1, PGC-1α, and Bcl-2 values decreased. All these changes were restored with DPG treatment.

Conclusion: DPG exhibited protective effects against inflammation, oxidative stress, and subsequent apoptosis observed in systemic inflammation-induced ALI likely through SIRT-1/ PGC-1α pathway.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive memory loss and cognitive decline. The processes underlying the pathophysiology of AD are still not fully understood despite a great deal of research. Since mitochondrial dysfunction affects cellular energy metabolism, oxidative stress, and neuronal survival, it is becoming increasingly clear that it plays a major role in the development of AD. This review summarizes the recent developments of mitochondrial dysfunction in AD, emphasizing mitochondrial biogenesis, dynamics, axonal transport, interactions between endoplasmic reticulum and mitochondria, mitophagy, and mitochondrial proteostasis. It emphasizes how tau and amyloid-beta (Aβ) proteins worsen mitochondrial and synaptic dysfunction by impairing adenosine triphosphate (ATP) synthesis, causing oxidative stress, and upsetting equilibrium. Additionally, important processes controlling mitochondrial activity and their correlation to the brain health are also discussed. One of the promising therapeutic approaches to lessen neurodegeneration and cognitive decline in AD is to improve mitochondrial activity. This study highlights possible directions for creating focused therapies to impede the advancement of AD through incorporating knowledge of mitochondrial biogenesis and its related mechanisms.

Background: The identification of circulating potential biomarkers may help earlier diagnosis of breast cancer, which is critical for effective treatment and better disease outcomes. We aimed to study the role of circ-FAF1 as a diagnostic biomarker in female breast cancer using peripheral blood samples of these patients, and to investigate the relation between circ-FAF1 and different clinicopathological features of the included patients.

Methods and results: This case-control study enrolled 60 female breast cancer patients and 60 age-matched healthy control subjects. For all study subjects, serum samples were collected for RNA extraction followed by reverse transcription and quantitative real time polymerase chain reaction for circ-FAF1 relative expression level. Serum circ-FAF1 was significantly downregulated in the studied patients compared to control subjects (p < 0.001). Low expression level of circ-FAF1 was significantly associated with presence of lymph node spread (p < 0.001), positive metastasis (p = 0.002), estrogen receptor negativity (p < 0.001), HER2 positivity (p < 0.001), and it was moderately correlated with higher Ki-67 index (r=-0.429, p = 0.001). However, circulating circ-FAF1 level had no statistically significant correlation with progesterone receptor status (p = 0.053), tumor histopathological type (p = 0.895) and histological grade (p = 0.369). Using ROC curve, serum circ-FAF1 had an AUC of 0.885, 81.67% diagnostic sensitivity and 76.67% diagnostic specificity.

Conclusion: Serum level of circ-FAF1 is a promising biomarker that can help in diagnosis of breast cancer. The low expression in breast cancer was correlated with lymph node spread, presence of metastasis, and with histopathological parameters suggestive of a worse outcome in these patients.

Background: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are associated with a multifactorial complicated aetiology that is often coexisting and has a strong and distinct connection with cardiovascular diseases (CVDs). In order to accomplish effective and appropriate therapeutic strategies, a deeper understanding of the bidirectional interaction between NAFLD patients, NAFLD patients with T2DM, and NAFLD patients with CVDs is required to control the concomitant rise in prevalence of these conditions worldwide. This article also aims to shed light on the epidemiology and mechanisms behind the relationship between T2DM, NAFLD and the related cardiovascular consequences.

Method: Literature was collected from PubMed, Medline, Embase, Web of Science and Google scholar from inception to June, 2024. For surveying literature different combinations and formats of terms including NAFLD, NASH, T2DM and CVDs were used.

Results: In the recent decade, clinical and epidemiological studies have been conducted and provide strong evidence that NAFLD is closely linked with CVD progression along with associated morbidity and mortality in both patients with and without T2DM. Several mechanistic approaches contribute to cardiovascular consequences and abnormalities in cardiac biomarkers in T2DM and NAFLD patients, including adipose tissue malfunction, mitochondrial dysfunction, the microbiota, genetic and epigenetic alterations contributing to insulin resistance, glucotoxicity and lipotoxicity.

Conclusion: The study reveals a complex interplay between diabetes, hepatic and cardiovascular complications, leading to significant morbidity and mortality in diabetic and NAFLD patients. This pandemic necessitates further research to identify mitigating variables and develop effective treatment approaches.

Background: Glyphosate is an extensively employed herbicide in agriculture, specifically for sugarcane cultivation. The situation is different with the extensive physiological and genetic effects exerted by this herbicide on a range of plant species, including sugarcane, whose model basis is still poorly characterized, although its primary mode of action, which acts on the EPSPS enzyme in the shikimic acid pathway, is completely elucidated. The current study was aimed at investigating the stability of glyphosate formulation, molecular interactions of glyphosate formulation with rbcL enzyme associated with chlorophyll metabolism, and its effects on varieties of sugarcane.

Methods and results: The stability of a ground-up glyphosate formulation was assessed under accelerated storage conditions. Molecular docking was performed to analyze interactions between glyphosate derivatives and rbcL. Two sugarcane varieties (G84-47 and GT54-9) were treated with increasing glyphosate concentrations (0.2, 0.4, and 0.8 mg L^-1) to evaluate effects on chlorophyll content, plant height, herbicide tolerance, and rbcL expression. The formulation showed good stability with minor degradation (47.55-47.14%). N-Nitrosoglyphosate and 2-(phosphonomethylamino)acetic acid exhibited favorable binding affinities with rbcL. Glyphosate treatment reduced chlorophyll content and plant height dose-dependently, with G84-47 showing higher sensitivity. GT54-9 demonstrated higher herbicide tolerance in survival analysis. rbcL expression remained stable in G84-47 but was significantly upregulated in GT54-9 under high herbicide stress.

Conclusions: This study reveals genetic variability in sugarcane responses to glyphosate, with variety-specific mechanisms underlying stress adaptation. The inducible rbcL expression in tolerant varieties provides insights into herbicide resistance mechanisms. These findings can inform marker-assisted breeding and improve agronomic practices for enhanced sugarcane cultivation resilience and sustainability.

Background: Litter size in mice is an important fitness and economic feature that is controlled by several genes and influenced by non-genetic factors too. High positive selection pressure in each generation for Litter size at birth (LSB), resulted in the development of high and low prolific lines of inbred Swiss albino mice (SAM). Despite uniform management conditions, these lines showed variability in LSB across the generation.

Methods and results: Variation in estrous-phased ovarian gene expression between high (LSB ≥ 12) and low prolific lines (LSB ≤ 3) of F₄ inbred SAM, was explored using RNA-Seq. Estrous phase assessment was done using vaginal cytology. A total of 870 differentially expressed genes (DEGs) were identified; among which, 287 genes were significantly up-regulated while 583 genes were down-regulated in HLS as compared to the LLS group. DEGs were assigned to 166 Gene Ontology (GO) terms and KEGG pathways. In HLS, the significantly up-regulated DEGs were involved in ovarian cell-cell signaling, regulation of biological activity and ovarian metabolic-associated pathways. Most down-regulated DEGs were expressed in immune-related pathways, indicating that immunological dampening is associated with a high ovulation rate and higher level of progesterone concentration leading to physiological changes responsible for higher fecundity.

Conclusions: The present study, based on bulk RNA-seq analysis reflects the aggregate gene expression of the whole ovarian tissue, and reveals 24 DEGs that could be used as candidates for litter size attributes in future polymorphism and functional studies to gain further insights into the mechanisms underlying litter size variations in animals.