The role of glypican-3 in hepatocellular carcinoma: Insights into diagnosis and therapeutic potential.

Glypican-3 (GPC-3) is predominantly found in the placenta and fetal liver, with limited expression in adult tissues. Its re-expression in hepatocellular carcinoma (HCC) and secretion into the serum highlights its potential as a diagnostic marker. GPC-3 is involved in important cellular processes such as proliferation, metastasis, apoptosis, and epithelial-mesenchymal transition through various signaling pathways including Wnt, IGF, YAP, and Hedgehog.

Unveiling the role of the Hedgehog signaling pathway in chronic liver disease: Therapeutic insights and strategies.

The Hedgehog (Hh) signaling plays a crucial role in adult liver repair by promoting the expansion and differentiation of hepatic progenitor cells into mature hepatocytes and cholangiocytes. Elevated Hh signaling is associated with severe chronic liver diseases, making Hh inhibitors a promising therapeutic option. Sonidegib and vismodegib, both FDA-approved Smoothened (Smo) inhibitors for basal cell carcinoma (BCC), have shown potential for application in chronic liver disorders based on clinical evidence.

Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence.

Hepatocellular carcinoma (HCC) is often recognized as an inflammation-linked cancer, which possesses an immunosuppressive tumor microenvironment. Curative treatments such as surgical resection, liver transplantation, and percutaneous ablation are mainly applicable in the early stage and demonstrate significant improvement of survival rate in most patients. However, 70-80% of patients report HCC recurrence within 5 years of curative treatment, representing an important clinical issue.

Kaempferide exhibits an anticancer effect against hepatocellular carcinoma in vitro and in vivo.

Context: Phytochemicals have been promising candidates for cancer therapy, affecting various cancer initiation and progression stages. Kaempferide is a mono methoxy flavone that shows potent anticancer effects on multiple cancers both in vitro and in vivo.

Materials And Methods: We evaluated the anticancer activity of kaempferide against HCC using an MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay.

Deciphering the role of transforming growth factor-beta 1 as a diagnostic-prognostic-therapeutic candidate against hepatocellular carcinoma.

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression. Among different ligands of the TGF-β family, TGF-β1 modulates most of its biological outcomes. Despite the abundant expression of TGF-β1 in the liver, steatosis to hepatocellular carcinoma (HCC) progression triggers elevated TGF-β1 levels, contributing to poor prognosis and survival.

Biology, Significance and Immune Signaling of Mucin 1 in Hepatocellular Carcinoma.

Mucin 1 (MUC 1) is a highly glycosylated tumor-associated antigen (TAA) overexpressed in hepatocellular carcinoma (HCC). This protein plays a critical role in various immune-mediated signaling pathways at its transcriptional and post-transcriptional levels, leading to immune evasion and metastasis in HCC. HCC cells maintain an immune-suppressive environment with the help of immunesuppressive tumor-associated antigens, resulting in a metastatic spread of the disease.

Harnessing the immune system against cancer: current immunotherapy approaches and therapeutic targets.

Cancer immunotherapy is a rapidly evolving concept that has been given the tag "fifth pillar" of cancer therapy while radiation therapy, chemotherapy, surgery and targeted therapy remain the other four pillars. This involves the stimulation of the immune system to control tumor growth and it specifically targets the neoplastic cells rather than the normal cells. Conventional chemotherapy has many limitations which include drug resistance, recurrence of cancer and severe adverse effects.

Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance.

An antibody-drug conjugate (ADC) is an advanced chemotherapeutic option with immense promises in treating many tumor. They are designed to selectively attack and kill neoplastic cells with minimal toxicity to normal tissues. ADCs are complex engineered immunoconjugates that comprise a monoclonal antibody for site-directed delivery and cytotoxic payload for targeted destruction of malignant cells.

Mucus targeting as a plausible approach to improve lung function in COVID-19 patients.

COVID-19 (SARS-CoV-2) has emerged as one of the worst pandemics that have tormented the globe due to its highly contagious nature. Even if the disease manifests fever-like symptoms mostly, the disease may progress to the pulmonary-hyper inflammatory phase, with severe pneumonia, hypoxia and subsequent multiple organ infection. This subsequently creates a huge burden to the health care systems across the globe for an immediate arrangement of ventilator facilities, oxygen supply and advanced health care.

Insights into an Immunotherapeutic Approach to Combat Multidrug Resistance in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has emerged as one of the most lethal cancers worldwide because of its high refractoriness and multi-drug resistance to existing chemotherapies, which leads to poor patient survival. Novel pharmacological strategies to tackle HCC are based on oral multi-kinase inhibitors like sorafenib; however, the clinical use of the drug is restricted due to the limited survival rate and significant side effects, suggesting the existence of a primary or/and acquired drug-resistance mechanism. Because of this hurdle, HCC patients are forced through incomplete therapy.

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review.

Chemopreventive approaches with food-derived phytochemicals are progressively rising as a significant aspect of tumor management and control. Herein, we have showcased the major phytoconstituents belonging to the group of flavanoid, as anti-cancer agents used for the treatment and prevention of hepatocellular carcinoma (HCC). Sorafenib is the sole drug used for the treatment of advanced HCC, but its clinical application is limited because of its severe adverse effects and drug resistance.

Unravelling the Immune Modulatory Effect of Indian Spices to Impede the Transmission of COVID-19: A Promising Approach.

Months after WHO declared COVID-19 as a Global Public Health Emergency of International Concern, it does not seem to be flattening the curve as we are still devoid of an effective treatment modality and vaccination is in the first phase in many countries. Amid such uncertainty, being immune is the best strategy to defend against corona attacks. As the whole world is referring back to immune-boosting traditional remedies, interest is rekindled in the Indian system of Medicine, which is gifted with an abundance of herbal medicines as well as remedies.

An insight into the role of telmisartan as PPAR-γ/α dual activator in the management of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease. It is rapidly emerging as the frequent cause for liver transplantation with the risk of disease recurrence, even after transplantation. Clinical evidence showed an abnormally altered expression of different peroxisome proliferator-activated receptor (PPAR) isotypes (PPAR-α/γ/δ) in NAFLD with an involvement in the induction of insulin resistance, hepatic steatosis, reactive oxygen species (ROS) formation, and hepatic inflammation.

Anti-VEGF Mediated Immunomodulatory Role of Phytochemicals: Scientific Exposition for Plausible HCC Treatment.

Hepatocellular carcinoma (HCC) is one of the most common solid tumours and the second leading cause of cancer-related mortality worldwide. Advanced-recurrent HCC often requires a systemic drug therapy where multi tyrosine kinase inhibitor, Sorafenib represents the first-line therapy option. But it exhibited very limited survival benefit and tumour response due to the early emergence of drug resistance and drug-related adverse effect.

The Impetus of COVID -19 in Multiple Organ Affliction Apart from Respiratory Infection: Pathogenesis, Diagnostic Measures and Current Treatment Strategy.

The pandemic spread of COVID 19 caused by the novel Coronavirus (SARS-CoV- 2) produced a tremendous effect on the life of humanity across the globe. The epidemiological studies revealed the drastic spectrum of SARS-CoV 2 infection ranging from mere flu-like symptoms to severe respiratory suppression within a short period. Initially, cases have been confined in the emerging point, Wuhan, China.

Search for Sterile Neutrinos in MINOS and MINOS+ Using a Two-Detector Fit.

A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 and 735 km, using a combined MINOS and MINOS+ exposure of 16.36×10^{20} protons on target.

Limits on Active to Sterile Neutrino Oscillations from Disappearance Searches in the MINOS, Daya Bay, and Bugey-3 Experiments.

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework.

Search for Sterile Neutrinos Mixing with Muon Neutrinos in MINOS.

We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a ν_{μ}-dominated beam with a peak energy of 3 GeV. The data, from an exposure of 10.

First Measurement of Electron Neutrino Appearance in NOvA.

We report results from the first search for ν_{μ}→ν_{e} transitions by the NOvA experiment. In an exposure equivalent to 2.74×10^{20} protons on target in the upgraded NuMI beam at Fermilab, we observe 6 events in the Far Detector, compared to a background expectation of 0.

Improved motor and cognitive performance with sodium nitrite supplementation is related to small metabolite signatures: a pilot trial in middle-aged and older adults.

Advancing age is associated with reductions in nitric oxide bioavailability and changes in metabolic activity, which are implicated in declines in motor and cognitive function. In preclinical models, sodium nitrite supplementation (SN) increases plasma nitrite and improves motor function, whereas other nitric oxide-boosting agents improve cognitive function. This pilot study was designed to translate these findings to middle-aged and older (MA/O) humans to provide proof-of-concept support for larger trials.

Effects of sodium nitrite supplementation on vascular function and related small metabolite signatures in middle-aged and older adults.

Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation with sodium nitrite, a precursor of NO, ameliorates age-related vascular endothelial dysfunction and arterial stiffness in mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose of this study was to determine the safety, feasibility, and efficacy of oral sodium nitrite supplementation for improving vascular function in middle-aged and older adults and to identify related circulating metabolites.

A Ground-Up Model for Gun Violence Reduction: A Community-Based Public Health Approach.

The suggested strategy for the reduction of violence is to collaboratively address the problem, based on an intervention system focused on prevention, rehabilitation, and development. This strategy is capable of engaging community residents in positive ways, and it empowers them to take ownership and sustain much-needed resident commitments to achieve long-term public safety. The community residents largely insist that over-reliance on law enforcement to control violence invites further affliction among Black youth and adults.

Combined analysis of νμ disappearance and νμ→νe appearance in MINOS using accelerator and atmospheric neutrinos.

We report on a new analysis of neutrino oscillations in MINOS using the complete set of accelerator and atmospheric data. The analysis combines the ν(μ) disappearance and ν(e) appearance data using the three-flavor formalism. We measure |Δm(32)(2)| = [2.

Inorganic nitrite supplementation for healthy arterial aging.

Aging is the major risk factor for cardiovascular diseases (CVD). This is attributable primarily to adverse changes in arteries, notably, increases in large elastic artery stiffness and endothelial dysfunction mediated by inadequate concentrations of the vascular-protective molecule, nitric oxide (NO), and higher levels of oxidative stress and inflammation. Inorganic nitrite is a promising precursor molecule for augmenting circulating and tissue NO bioavailability because it requires only a one-step reduction to NO.