Hepatocellular Carcinoma (HCC) is a highly aggressive cancer with mortality running parallel to its incidence and has limited therapeutic options. Chronic liver inflammation and injury contribute significantly to the development and progression of HCC. Several factors such as gender, age, ethnicity, and demographic regions increase the HCC incidence rates and the major risk factors are chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), carcinogens (food contaminants, tobacco smoking, and environmental toxins), and inherited diseases. In recent years evidence highlights the association of metabolic syndrome (diabetes and obesity), excessive alcohol consumption (alcoholic fatty liver disease), and high-calorie intake (nonalcoholic fatty liver disease) to be the prime causes for HCC in countries with a westernized sedentary lifestyle. HCC predominantly occurs in the setting of chronic liver disease and cirrhosis (80%), however, 20% of the cases have been known in patients with non-cirrhotic liver. It is widely believed that there exist possible interactions between different etiological agents leading to the involvement of diverse mechanisms in the pathogenesis of HCC. Understanding the molecular mechanisms of HCC development and progression is imperative in developing effective targeted therapies to combat this deadly disease. Noteworthy, a detailed understanding of the risk factors is also critical to improve the screening, early detection, prevention, and management of HCC. Thus, this review recapitulates the etiology of HCC focusing especially on the nonalcoholic fatty liver disease (NAFLD)- and alcoholic fatty liver disease (AFLD)-associated HCC.

/pdf/etiology-of-hepatocellular-carcinoma-special-focus-on-fatty-2xleftzwfj.pdf

Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease.

Background and aims Accumulating studies identified that BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is integrally involved in the initiation and development of tumors. Nevertheless, the precise biological role and underlying mechanisms of BUB1B in hepatocellular carcinoma (HCC) remain indistinct. Method To figure out the role of BUB1B in HCC, we first assessed its expression using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then verified BUB1B expression in HCC tissues, nontumor tissues, and HCC cell lines through western blotting, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. To explore the specific function of BUB1B in HCC in vivo and in vitro, we performed the flow cytometry, Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, colony formation, Transwell, wound-healing, subcutaneous tumor growth, and metastasis assays. Additionally, we identified the BUB1B-regulated pathways involved in HCC by using gene set enrichment analysis. Results Our data displayed that higher BUB1B expression was detected in HCC tissues and HCC cell lines. The overexpression of BUB1B was positively correlated with adverse clinicopathological characteristics. Survival analyses showed that lower recurrence-free and overall survival rates were correlated with the overexpression of BUB1B in patients with HCC. Moreover, the malignancy of HCC was facilitated by BUB1B both in vivo and in vitro. Lastly, the results were confirmed by western blots, which showed that BUB1B upregulated mTORC1 signaling pathway in HCC. Meanwhile, the oncogenic effect of BUB1B will be impaired when the mTORC1 signaling pathway was inhibited by rapamycin. Conclusion We highlighted that BUB1B played an oncogenic role in HCC and was identified as a possible clinical prognostic factor and a potential novel therapeutic target for HCC.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.3411

BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway.

Chronic or non-communicable diseases are the leading cause of death worldwide; they usually result in long-term illnesses and demand long-term care. Despite advances in molecular therapeutics, specific biomarkers and targets for the treatment of these diseases are required. The dysregulation of de novo lipogenesis has been found to play an essential role in cell metabolism and is associated with the development and progression of many chronic diseases; this confirms the link between obesity and various chronic diseases. The main enzyme in this pathway-ATP-citrate lyase (ACLY), a lipogenic enzyme-catalyzes the critical reaction linking cellular glucose catabolism and lipogenesis. Increasing lines of evidence suggest that the modulation of ACLY expression correlates with the development and progressions of various chronic diseases such as neurodegenerative diseases, cardiovascular diseases, diabetes, obesity, inflammation, and cancer. Recent studies suggest that the inhibition of ACLY activity modulates the glycolysis and lipogenesis processes and stimulates normal physiological functions. This comprehensive review aimed to critically evaluate the role of ACLY in the development and progression of different diseases and the effects of its downregulation in the prevention and treatment of these diseases.

The vital role of ATP citrate lyase in chronic diseases

Type 2 Diabetes Prevention Diet and Hepatocellular Carcinoma Risk in US Men and Women.

Accumulating evidence indicates a strong correlation between type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC), but the underlying pathophysiology is still elusive. We aimed to identify unrecognized but important genes and pathways related to T2DM and HCC by bioinformatic analysis. The GSE64998 and GSE15653 datasets (for T2DM), the GSE121248 dataset and the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset (for HCC) were downloaded. Differential expression analysis, functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction, survival analysis, transcription factor (TF) prediction, and correlation of gene expression with methylation and tumour-infiltrating immune cells were conducted. Nine genes, namely, CDNF, CRELD2, DNAJB11, DTL, GINS2, MANF, PDIA4, PDIA6, and VCP, were recognized as hub genes. Enrichment analysis revealed several enriched terms and pathways. Transcription factors such as Kruppel-like factor 6, abnormal methylation and immune dysregulation might help explain the dysregulation of hub genes. Our study identified nine hub genes that might play a critical role in both T2DM and HCC. However, more studies are warranted to clarify the mechanisms of these genes.

Key genes associated with diabetes mellitus and hepatocellular carcinoma.

Diabetes and hepatocellular carcinoma: A pathophysiological link and pharmacological management.

In present scenario, stress is a common problem which affects not only elders, but also to older and youngster. Long term stress can be detrimental and causes various diseases related to CNS, immune system, neuro-endocrine system, liver, blood, learning, memory defeat and irregular sleeping pattern. A combined approach of traditional and modern system i.e., adaptogens help to overcome the stress and stress related problems. Adaptogens are generally the plant-derived biologically active substances that help to increase the body resistance against physical, biological, emotional and environmental stressors in nonspecific manner through maintenance of internal homeostasis. Adaptogenic herbs exhibit neuro-protective, anxiolytic, anti-fatigue, nootropic, anti-depressive, and CNS stimulating activity. Non-specific action of the adaptogenic herbs decreases the targeted phenomenon and efficiency so that more study, research and clinical trials are required to find the targeted action of adaptogens. In recent years, focus has been shifted towards the adaptogens due to its safety, cost effectiveness and efficacy for maintaining and improving the quality of life. The present review focuses on the mechanism of stress induction, its relation with anxiety, depression and immune system. It also highlights the different herbal biomolecules as an adaptogens that are used in either Ayurveda or Traditional Chinese Medicine [TCM].

https://www.longdom.org/open-access/biomolecules-from-plants-as-an-adaptogen-2155-9821-1000307.pdf

Biomolecules from Plants as an Adaptogen

Immunology is a branc h of biomedical science that involves all aspects of the immune system that recognize pathogens and initiate defense response that involve induction, expression, amplification or inhibition of phase of the immune response . Plant based medicines have potent ial immunomodulatory activity that can justify their use in past . Ferulic acid ( FA ) is a polyphenol abundant in several plants, possesses activity, such as antioxidant, antimicrobial, anti - inflammatory, anti - thrombosis, anti - cancer and also used in age - rel ated diseases such as neurodegenerative disorders, cardiovascular diseases and diabetes . The study was proposed to determine immunomodulatory effects of FA . Assessment of immunomodulatory activity of FA was done by carbon clearance test, delayed type hyper sensitivity ( DTH ) reaction, neutrophils adhesion test, e ffect on serum immunoglobulins and cyclophosphamide induced neutropenia . FA at doses 200 mg / kg p roduced significant increase in phagocytic index ( P<0 . 01 ) which indicated stimulation of reticuloendothe lial system, neutrophil count ( P<0 . 05 ) in nylon fibers which causes the stimulation of neutrophils towards the site of inflammation, the serum immunoglobulin levels ( P<0 . 05 ) shows direct measure of T and B cell activity, TLC count ( P<0 . 05 ) and prevent n eutropenia through activation of macrophages and increase in DTH response ( P<0 . 05 ) which indicate stimulatory effect on lymphocyte . On the basis of present investigation, it can be concluded that FA has potential to stimulate overall immune system in the experimental animals .

http://www.irjponline.com/admin/php/uploads/2466_pdf.pdf

In vivo evaluation of immunomodulatory potential of ferulic acid

Objective: The objective of the current study was carried out to investigate the effects of methanolic extract of Buchanania lanzan Spreng seeds on hematological indices. Materials and Methods: Eighteen male albino Wistar rats were divided into three groups, six in each. Group I animals received distilled water, Group II and III were treated with an oral dose of 1000 mg oil/kg and 2000 mg oil/kg of extract, respectively, for 7 days. At the end of the study, blood was collected and evaluated for packed cell volume (PCV), hemoglobin (Hb) concentration, and red blood cell (RBC) and white blood cell (WBC) counts. Results: There was a significant dose-dependent increase in the hematological indices such as PCV, Hb, RBC, and WBC count in the treatment group. Conclusions: The improvement of PCV, Hb, and RBC values is an indication of the anti-anemic effect which may be due to the stimulation of RBC production in bone marrow. Further, stimulated production of WBC could be as a result of possible stimulus of the immune system. Hence, this study confirms that the extract of B. lanzan could be useful for the treatment of anemia.

The effect of methanolic extract of Buchanania lanzan Spreng seeds on hematological indices.

A solemn gastrointestinal disorder, peptic ulcer represented by erosions in mucosal linings of stomach and duodenum entailed for a well targeted remedial agent . Numerous drugs acting for the treat ment of peptic ulcer is available, but limitations ( side effects, occurrence of relapses, drug interactions ) of these agents have focused and shifted the search for a novel molecules ensuring better protection and with minimal side effects . Herbal based fo rmulations of medicinal plants are gaining popularity which being on focus, thereby ensur es for a better treatment of ulcer . A combination of modern research with the Ayurvedic ( herbal based plants ) knowledge is in need ed to develop standard procedures for standardization of herbs for anti - ulcer activity . The present review focuses on the different medicinal plants having gastroprotective activity .

http://www.irjponline.com/admin/php/uploads/2458_pdf.pdf

Potential gastroprotective medicinal plants : an overview

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