RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA ...activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA‐RhoGDI complex exists in the cytosol and the active GTP‐bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA‐GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA‐RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c‐Myc, HIF‐1α/2α, Stat 6, and NF‐κB along with several reported microRNAs. As the role of RhoA in regulating actin‐filament formation and myosin‐actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F‐actin)‐dependent (“actin switch”) or—independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP‐1, NF‐κB, YAP/TAZ, β‐catenin, and hypoxia inducible factor (HIF)‐1α. Interestingly, RhoA also itself is localized to the nucleus by an as‐yet‐undiscovered mechanism.
We descibed the regulation of RhoA activity and expression levels. In addition, we described transcription factors which are regulated by RhoA.
Bioactive plant derived compounds are important for a wide range of therapeutic applications, and some display promising anticancer properties. Further evidence suggests that phytochemicals modulate ...autophagy and apoptosis, the two crucial cellular pathways involved in the underlying pathobiology of cancer development and regulation. Pharmacological targeting of autophagy and apoptosis signaling using phytochemicals therefore offers a promising strategy that is complementary to conventional cancer chemotherapy. In this review, we sought to highlight the molecular basis of the autophagic-apoptotic pathway to understand its implication in the pathobiology of cancer, and explore this fundamental cellular process as a druggable anticancer target. We also aimed to present recent advances and address the limitations faced in the therapeutic development of phytochemical-based anticancer drugs.
Insulin is a crucial signalling molecule that primarily functions to reduce blood glucose levels through cellular uptake of glucose. In addition to its role in glucose homeostasis, insulin has been ...shown to regulate cell proliferation. Specifically, insulin enhances the phosphorylation of pyruvate dehydrogenase E1α (PDHA1) at the Ser293 residue and promotes the proliferation of HepG2 hepatocellular carcinoma cells. Furthermore, we previously observed that p-Ser293 PDHA1 bound with pyruvate kinase M2 (PKM2) as confirmed by coimmunoprecipitation. In this study, we used an in silico analysis to predict the structural conformation of the two binding proteins. However, the function of the protein complex remained unclear. To investigate further, we treated cells with si-PDHA1 and si-PKM2, which led to a reduction in PKM2 and p-Ser293 PDHA1 levels, respectively. Additionally, we found that the PDHA S293A dephospho-mimic reduced PKM2 levels and its associated enzyme activity. Treatment with MG132 and leupeptin impeded the PDHA1 S293A-mediated PKM2 reduction. These results suggest that the association between p-PDHA1 and PKM2 promotes their stability and protects them from protein degradation. Of interest, we observed that p-PDHA1 and PKM2 were localized in the nucleus in liver cancer patients. Under insulin stimulation, the knockdown of both PDHA1 and PKM2 led to a reduction in the expression of common genes, including KDMB1. These findings suggest that p-PDHA1 and PKM2 play a regulatory role in these proteins’ expression and induce tumorigenesis in response to insulin.
Purpose: Poultry manure (PM) is a concern for Bangladesh. The improvement of quality and safety is always desirable. The experiment assesses the quality and safety parameters of PM with the addition ...of Saccharomyces cerevisiae and indigenous microorganisms (IMO) in different fermentation conditions (aerobic, facultative anaerobic, and anaerobic) for 7 days. Method: Fermentation condition × treatment factorial analyses were performed to explore their effect on the quality and safety of PM. The organoleptic quality (color, smell, and texture), pH, nutritional components (organic matter, crude fiber, crude protein, ether extract, nitrogen-free extract), in-vitro organic matter digestibility, metabolizable energy, mineral contents (phosphorus, potassium, sulfur), heavy metals (lead, copper), and microbial properties (total coliform count, E-coli, Salmonella) of fermented PM at 0, 3, 5, and 7 days were evaluated. Results: All parameters of the different treatments in different fermentation conditions changed significantly (P < 0.05) with increasing the fermentation time. All parameters were found desirable in 10% IMO treated PM. Organoleptic parameters (color, smell, and texture) were satisfactory in aerobic fermentation but other parameters were acceptable in anaerobic fermentation conditions. pH was dropped significantly (P < 0.05) with increasing the duration. Conclusion: To summarize all properties, it could be noted that the quality and safety of PM were improved after 7 days of fermentation with a fermentation mixture of PM (90%) and molasses (10%) inoculating 10% IMO under an anaerobic condition which could be used for animal feeding. Research Highlights: Utilization of poultry manure by fermentation process Use of Saccharomyces cerevisiae and indigenous microorganisms (IMO) Improving quality and safety as ruminant feed
The key tumor suppressor protein p53, additionally known as p53, represents an attractive target for the development and management of anti-cancer therapies. p53 has been implicated as a tumor ...suppressor protein that has multiple aspects of biological function comprising energy metabolism, cell cycle arrest, apoptosis, growth and differentiation, senescence, oxidative stress, angiogenesis, and cancer biology. Autophagy, a cellular self-defense system, is an evolutionarily conserved catabolic process involved in various physiological processes that maintain cellular homeostasis. Numerous studies have found that p53 modulates autophagy, although the relationship between p53 and autophagy is relatively complex and not well understood. Recently, several experimental studies have been reported that p53 can act both an inhibitor and an activator of autophagy which depend on its cellular localization as well as its mode of action. Emerging evidences have been suggested that the dual role of p53 which suppresses and stimulates autophagy in various cencer cells. It has been found that p53 suppression and activation are important to modulate autophagy for tumor promotion and cancer treatment. On the other hand, activation of autophagy by p53 has been recommended as a protective function of p53. Therefore, elucidation of the new functions of p53 and autophagy could contribute to the development of novel therapeutic approaches in cancer biology. However, the underlying molecular mechanisms of p53 and autophagy shows reciprocal functional interaction that is a major importance for cancer treatment and manegement. Additionally, several synthetic drugs and phytochemicals have been targeted to modulate p53 signaling via regulation of autophagy pathway in cancer cells. This review emphasizes the current perspectives and the role of p53 as the main regulator of autophagy-mediated novel therapeutic approaches against cancer treatment and managements.
Aggressive and recurrent gynecological cancers are associated with worse prognosis and a lack of effective therapeutic response. Ovarian cancer (OC) patients are often diagnosed in advanced stages, ...when drug resistance, angiogenesis, relapse, and metastasis impact survival outcomes. Currently, surgical debulking, radiotherapy, and/or chemotherapy remain the mainstream treatment modalities; however, patients suffer unwanted side effects and drug resistance in the absence of targeted therapies. Hence, it is urgent to decipher the complex disease biology and identify potential biomarkers, which could greatly contribute to making an early diagnosis or predicting the response to specific therapies. This review aims to critically discuss the current therapeutic strategies for OC, novel drug-delivery systems, and potential biomarkers in the context of genetics and molecular research. It emphasizes how the understanding of disease biology is related to the advancement of technology, enabling the exploration of novel biomarkers that may be able to provide more accurate diagnosis and prognosis, which would effectively translate into targeted therapies, ultimately improving patients' overall survival and quality of life.
Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. ...Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, and malignancies. Recently, natural compounds have come to attention for being able to modulate the autophagy pathway in cancer prevention, although the prospective role of autophagy in cancer treatment is very complex and not yet clearly elucidated. Numerous synthetic chemicals have been identified that modulate autophagy and are favorable candidates for cancer treatment, but they have adverse side effects. Therefore, different phytochemicals, which include natural compounds and their derivatives, have attracted significant attention for use as autophagy modulators in cancer treatment with minimal side effects. In the current review, we discuss the promising role of natural compounds in modulating the autophagy pathway to control and prevent cancer, and provide possible therapeutic options.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function and neuronal damage. Although the precise pathobiology of AD remains elusive, ...accumulating evidence suggests that mitochondrial dysfunction is one of the underlying causes of AD. Mutations in mitochondrial or nuclear DNA that encode mitochondrial components may cause mitochondrial dysfunction. In particular, the dysfunction of electron transport chain complexes, along with the interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunction in AD. Mitochondrial dysfunction causes an imbalance in the production of reactive oxygen species, leading to oxidative stress (OS) and vice versa. Neuroinflammation is another potential contributory factor that induces mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense systems, thereby protecting against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Therefore, pharmacological intervention via neuroprotective phytochemicals can be a potential strategy to combat mitochondrial dysfunction as well as AD. This review focuses on the role of phytochemicals in mitigating mitochondrial dysfunction in the pathogenesis of AD.
Background & Importance: Atlas assimilation is the congenital Atlas fusion with the base of the occipital bone. Case Presentation: A patient was presented with neck pain, dysaesthesia and tingling of ...hands and feet and difficulty in walking for 4 years. On examinations, the patient had a short neck with rigidity in neck muscles and there were exaggerated jerks with bilateral Babinski sign. Cervical spinal x-ray indicated basilar invagination with the absence of a C1 arch and CT scan of the cervical spine showed assimilation of C1 with basilar invagination. Occipitocervical stabilization has been commonly proposed for the operational fusion. The iliac crest interposing bone graft was performed for fusion and stabilization of the occipitocervical region. The patient was treated surgically and soon after operation became painless and was able to move easily. Conclusion: In C1 assimilation with basilar invagination, bicortical occipital screws and C2 pedicle screws with interposition bone graft can be the way to optimize the shortest segmental stabilization and fusion procedure for occipitocervical fusion.
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