Effect of Lauric acid against ethanol-induced hepatotoxicity by modulating oxidative stress/apoptosis signalling and HNF4α in Wistar albino rats.

Ethanol (EtOH) is most widely used in alcoholic beverages to prepare alcohol. As EtOH is mainly metabolised in the liver, the excessive consumption of EtOH forms a primary toxic metabolic product called acetaldehyde, as the gradual increase in acetaldehyde leads to liver injury, as reported. Lauric acid (LA) is rich in antioxidant, antifungal, antibacterial, anticancer, and antiviral properties. LA is an edible component highly present in coconut oil. However, no report on LA protective effects against the EtOH-instigated hepatotoxicity exists. Therefore, the experiment is carried out to investigate the potency effects of LA on EtOH-instigated hepatotoxicity in thirty male albino rats. Rats were divided into five groups (n-6): control DMSO alone, EtOH -intoxicated, EtOH + LA 180 mg/kg, EtOH + LA 360 mg/kg, and LA alone were administered orally using oral gavage. The study measured body weight every weekend in all rat groups. The rats were sacrificed and assessed for serum markers (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase), antioxidant activity (superoxide dismutase, reduced glutathione, glutathione peroxidase), lipid peroxidation (malondialdehyde), histopathological, cytokine levels (TNF-α, IL-1ß and IL-6), protein expression (caspase 3 and caspase 8 and Bcl-2 and HNF4α) were evaluated after the 56-days study period. The impact of EtOH intoxication reduces the rat's body weight by 90 g, upregulates the liver enzyme markers, depletes the antioxidant levels, produces malondialdehyde, changes the histoarchitecture (periportal inflammation and hepatocyte damage), downregulates the Bcl-2 expressions and HNF4α, and elevates the expression of cytokines and apoptotic markers. LA alleviated EtOH-induced liver toxicity by significant (p < 0.05) modulation of biochemical levels, caspase-8/3 signalling, reducing pro-inflammatory cytokines, and restoring the normal histoarchitecture, upregulating the Bcl-2 and HNF4α Expressions. In conclusion, LA treatment can protect the liver against EtOH-induced hepatotoxicity, evidenced by alleviating Oxidative stress, lipid peroxidation, inflammation, apoptosis, and upregulation of HNF4α.

Novel biomolecules in targeted cancer therapy: a new approach towards precision medicine.

Cancer is a major threat to human life around the globe, and the discovery of novel biomolecules continue to be an urgent therapeutic need that is still unmet. Precision medicine relies on targeted therapeutic strategies. Researchers are better equipped to develop therapies that target proteins as they understand more about the genetic alterations and molecules that cause progression of cancer. There has been a recent diversification of the sorts of targets exploited in treatment. Therapeutic antibody and biotechnology advancements enabled curative treatments to reach previously inaccessible sites. New treatment strategies have been initiated for several undruggable targets. The application of tailored therapy has been proven to have efficient results in controlling cancer progression. Novel biomolecules like SMDCs, ADCs, mABs, and PROTACS has gained vast attention in the recent years. Several studies have shown that using these novel technology helps in reducing the drug dosage as well as to overcome drug resistance in different cancer types. Therefore, it is crucial to fully untangle the mechanism and collect evidence to understand the significance of these novel drug targets and strategies. This review article will be discussing the importance and role of these novel biomolecules in targeted cancer therapies.

HPV-associated cancers: insights into the mechanistic scenario and latest updates.

Cancer and related diseases are the second leading cause of death worldwide. The human papillomavirus (HPV) is an infectious agent that can be spread mainly through sexual contact and has been linked to several malignancies in both sexes. HPV is linked to almost all cases of cervical cancer. It is also linked to many head and neck cancer (HNC) cases, especially oropharyngeal cancer. Also, some HPV-related cancers, like vaginal, vulvar, penile, and anal cancers, are related to the anogenital area. Over the past few decades, testing for and preventing cervical cancer has improved, but anogenital cancers are still harder to confirm. HPV16 and HPV18 have been extensively researched due to their significant carcinogenic potential. The products of two early viral genes, E6 and E7, have been identified as playing crucial roles in cellular transformation, as emphasized by biological investigations. The complete characterization of numerous mechanisms employed by E6 and E7 in undermining the regulation of essential cellular processes has significantly contributed to our comprehension of HPV-induced cancer progression. This review focuses on the various types of cancers caused by HPV infection and also sheds light on the signaling cascades involved in the same.

Insights into the Scenario of SARS-CoV-2 Infection in Male Reproductive Toxicity.

COVID-19 has become a significant public health concern that has catastrophic consequences for society. Some preliminary evidence suggests that the male reproductive system may be an infection target for SARS-CoV-2. SARS-CoV-2 may be transmitted sexually, according to preliminary research. Testicular cells exhibit a high level of the angiotensin-converting enzyme 2 (ACE2) receptor, which enhances the entry of the SARS-CoV-2 into host cells. Some instances of COVID-19 have been documented to exhibit hypogonadism during the acute stage. Furthermore, systemic inflammatory reactions triggered by SARS-CoV-2 infection may cause oxidative stress (OS), which has been shown to have profoundly deleterious consequences on testicular functioning. This work gives a clear picture of how COVID-19 may affect male reproductive systems and calls attention to the many unanswered questions about the mechanisms by which this virus can be linked to men's health and fertility.

A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer.

Lung cancer (LC) is considered as one of the leading causes of cancer-associated mortalities. Cancer cells' reprogrammed metabolism results in changes in metabolite concentrations, which can be utilized to identify a distinct metabolic pattern or fingerprint for cancer detection or diagnosis. By detecting different metabolic variations in the expression levels of LC patients, this will help and enhance early diagnosis methods as well as new treatment strategies. The majority of patients are identified at advanced stages after undergoing a number of surgical procedures or diagnostic testing, including the invasive procedures. This could be overcome by understanding the mechanism and function of differently regulated metabolites. Significant variations in the metabolites present in the different samples can be analyzed and used as early biomarkers. They could also be used to analyze the specific progression and type as well as stages of cancer type making it easier for the treatment process. The main aim of this review article is to focus on rewired metabolic pathways and the associated metabolite alterations that can be used as diagnostic and therapeutic targets in lung cancer diagnosis as well as treatment strategies.

Crosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory disorder. Various organ injuries have been reported in response to this virus, including kidney injury and, in particular, kidney tubular injury. It has been discovered that infection with the virus does not only cause new kidney disease but also increases treatment difficulty and mortality rates in people with kidney diseases. In individuals hospitalized with COVID-19, urinary metabolites from several metabolic pathways are used to distinguish between patients with acute kidney injury (AKI) and those without. This review summarizes the pathogenesis, pathophysiology, treatment strategies, and role of metabolomics in relation to AKI in COVID-19 patients. Metabolomics is likely to play a greater role in predicting outcomes for patients with kidney disease and COVID-19 with varying levels of severity in the near future as data on metabolic profiles expand rapidly. Here, we also discuss the correlation between COVID-19 and kidney diseases and the available metabolomics approaches.

The Implication of Mechanistic Approaches and the Role of the Microbiome in Polycystic Ovary Syndrome (PCOS): A Review.

As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women's reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota composition and disruptions in secondary bile acid production appear to play a causative role in developing PCOS. PCOS pathophysiology and phenotypes are tightly related to both enteric and vaginal bacteria. Patients with PCOS exhibit changed microbiome compositions and decreased microbial diversity. Intestinal microorganisms also alter PCOS patient phenotypes by upregulating or downregulating hormone release, gut-brain mediators, and metabolite synthesis. The human body's gut microbiota, also known as the "second genome," can interact with the environment to improve metabolic and immunological function. Inflammation is connected to PCOS and may be caused by dysbiosis in the gut microbiome. This review sheds light on the recently discovered connections between gut microbiota and insulin resistance (IR) and the potential mechanisms of PCOS. This study also describes metabolomic studies to obtain a clear view of PCOS and ways to tackle it.

The pathophysiological and immunological background of the monkeypox virus infection: An update.

In addition to the COVID-19 waves, the globe is facing global monkeypox (MPX) outbreak. MPX is an uncommon zoonotic infection characterized by symptoms similar to smallpox. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus that belongs to the genus Orthopoxvirus (OPXV). MPXV, which causes human disease, has been confined to Africa for many years, with only a few isolated cases in other areas. Outside of Africa, the continuing MPXV outbreak in multiple countries in 2022 is the greatest in recorded history. The current outbreak, with over 10 000 confirmed cases in over 50 countries between May and July 2022, demonstrates that MPXV may travel rapidly among humans and pose a danger to human health worldwide. The rapid spread of such outbreaks in recent times has elevated MPX to the status of a rising zoonotic disease with significant epidemic potential. While the MPXV is not as deadly or contagious as the variola virus that causes smallpox, it poses a threat because it could evolve into a more potent human pathogen. This review assesses the potential threat to the human population and provides a brief overview of what is currently known about this reemerging virus. By analyzing the biological effects of MPXV on human health, its shifting epidemiological footprint, and currently available therapeutic options, this review has presented the most recent insights into the biology of the virus. This study also clarifies the key potential causes that could be to blame for the present MPX outbreak and draw attention to major research questions and promising new avenues for combating the current MPX epidemic.

Exploring the Regulatory Role of ncRNA in NAFLD: A Particular Focus on PPARs.

Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD.

Role of Immune Cells and Receptors in Cancer Treatment: An Immunotherapeutic Approach.

Cancer immunotherapy moderates the immune system's ability to fight cancer. Due to its extreme complexity, scientists are working to put together all the puzzle pieces to get a clearer picture of the immune system. Shreds of available evidence show the connection between cancer and the immune system. Immune responses to tumors and lymphoid malignancies are influenced by B cells, γδT cells, NK cells, and dendritic cells (DCs). Cancer immunotherapy, which encompasses adoptive cancer therapy, monoclonal antibodies (mAbs), immune checkpoint therapy, and CART cells, has revolutionized contemporary cancer treatment. This article reviews recent developments in immune cell regulation and cancer immunotherapy. Various options are available to treat many diseases, particularly cancer, due to the progress in various immunotherapies, such as monoclonal antibodies, recombinant proteins, vaccinations (both preventative and curative), cellular immunotherapies, and cytokines.

Exploring the Molecular Pathogenesis, Pathogen Association, and Therapeutic Strategies against HPV Infection.

The human papillomavirus (HPV), commonly documented as the cause of warts, has gained much interest recently due to its possible links to several types of cancer. HPV infection is discussed in this review from multiple angles, including its virology, epidemiology, etiology, immunology, clinical symptoms, and treatment. Recent breakthroughs in molecular biology have led to the development of new methods for detecting and treating HPV in tissue. There is no cure for HPV, and although vaccines are available to prevent infection with the most common HPV viruses, their utilization is limited. Destruction and excision are the primary treatment modalities. This review sheds light on the epidemiology, molecular pathogenesis, the association of several other pathogens with HPV, the latest treatment strategies available to treat the same, and an overview of the progress made and the obstacles still to be overcome in the fight against HPV infection.

A review on molecular mechanism of alcoholic liver disease.

Excessive alcohol consumption leads to damage to the organs of the body. More importantly, the liver is majorly affected organ upon alcohol consumption for most of the people; it causes inflammation and affects various pathways involved in metabolism. If the person is with high response of inflammatory in conduct with alcohol leads to the liver damage, which involves the creating effects with major cycle leads to homeostasis. In this review, we summarize the molecular mechanisms of alcoholic liver disease, such as the important role of genes, risk factors, pathogenicity, and role of micro RNA, the role of inflammation in the liver, and alcoholic fibrosis in the liver. There is increased oxidative stress, change in the biochemical alterations, and reduction in the antioxidant enzymes. These changes in the mechanism lead to liver injury. Hepatocyte nuclear factor-4 is the major transcriptional factor for the regulation of some genes involved in the lipid metabolism and oxidation process; with the help of the agonist, we can attenuate the level of the gene in the site of hepatic tissues, which will prevent the homeostatic condition. This review shows a clear view of the various pathways involved in alcohol consumption, which helps in the prevention of ALD using an agonist.

An appraisal on molecular and biochemical signalling cascades during arsenic-induced hepatotoxicity.

Arsenic is a ubiquitous metalloid compound commonly found in the environment, and it is usually found in combination with sulphur and metals. Arsenic is considered as a therapeutic as well as poisoning agent since ancient times. It causes toxic effects on different organs, mainly the liver. In this review, we focused on the molecular mechanism of arsenic-induced hepatotoxicity. Here we envisaged the bridge between arsenic and hepatotoxicity with particular focus on the level of hepatic enzymes such as ALT, AST, and ALP. Here, we attempted to elucidate the role of arsenic in redox imbalance on increased oxidative stress (elevated level of ROS, MDA and NO) and decreased antioxidant levels such as reduced GSH, catalase, and SOD. Oxidative stress induces mitochondrial dysfunction via apoptosis (AKT-PKB, MAPK, PI3/AKT, PKCδ-JNK, AKT/ERK, p53 pathways), fibrosis (TGF-ß/Smad pathway), and necrosis and inflammation (TNF-α, NF-ĸB, IL-1, and IL-6). Along with that, arsenic activates caspases and Bax, decreases Bcl2 through mitochondrial dysfunction, and induces apoptosis regulatory mechanism. We believe the alteration of all these pathways leads to arsenic-induced hepatotoxicity.

Protective effect of the ethanolic and methanolic leaf extracts of Madhuca longifolia against diclofenac-induced toxicity in female Wistar albino rats.

BACKGROUND: Diclofenac is commonly prescribed Non-Steroidal Anti-Inflammatory Drug (NSAIDs) as it has anti-inflammatory, analgesic and anti-pyretic properties. Long term usage and over-dosage of diclofenac is associated with adverse effects like drug-induced liver injury, gastrointestinal and renal toxicity. The therapeutic uses of medicinal plants have gained a prominent role in recent years. Madhuca longifolia is a tree found throughout India, which is known to have several pharmacological activities. The aim of our study is to investigate the potential effect of the ethanolic and methanolic leaf extracts of M. longifolia against diclofenac-induced toxicity. METHODS: The rats used for the experiment were divided into seven groups. Group-1 was the normal control. Group-2 was administered with diclofenac (50 mg/kg b.w./day/ip) on the 4th and the 5th day. Group-3 was treated with diclofenac and ELEML (500 mg/kg b.w./day/po) on all 5 days. Group-4 was treated with diclofenac and MLEML (500 mg/kg b.w./day/po) on all 5 days. Standard drug silymarin (25 mg/kg b.w./day/po) was given to the rats of group-5 along with diclofenac. Group-6 and group-7 were treated with ethanolic leaf extract and methanolic leaf extract of M. longifolia respectively. After the study period, the rats were evaluated for parameters like liver and renal markers, antioxidants and histopathological changes. RESULTS: This study has proved the beneficial effect of ethanolic and methanolic leaf extract of M. longifolia against diclofenac-induced toxicity wherein ethanolic leaf extract showed a better result than methanolic leaf extract. CONCLUSION: Our study has concluded the beneficial effect of ethanolic and methonolic leaf extract of Madhuca longifolia against DFC-induced toxicity. This study proves that it has potential effect on hepato, renal and gastro toxicity in female Wistar albino rats. It can further be studied to understand its mechanism in treating toxicity.