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These results may offer appropriate targets, such as FASN, for dietary intervention and/or chemoprevention to reduce PCa incidence and progression.Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this review, we attempt to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators including small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of various diseases.Lung cancer still contributes to nearly one-quarter cancer-related deaths in the past decades, despite the rapid development of targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC). The development and availability of comprehensive genomic profiling make the classification of NSCLC more precise and personalized. Most treatment decisions of advanced-stage NSCLC have been made based on the genetic features and PD-L1 expression of patients. For the past 2 years, more than 10 therapeutic strategies have been approved as first-line treatment for certain subgroups of NSCLC. However, some major challenges remain, including drug resistance and low rate of overall survival. Therefore, we discuss and review the therapeutic strategies of NSCLC, and focus on the development of targeted therapy and immunotherapy in advanced-stage NSCLC. Based on the latest guidelines, we provide an updated summary on the standard treatment for NSCLC. At last, we discussed several potential therapies for NSCLC. The development of new drugs and combination therapies both provide promising therapeutic effects on NSCLC.Over the last decades, the growing understanding on DNA damage response (DDR) pathways has broadened the therapeutic landscape in oncology. It is becoming increasingly clear that the genomic instability of cells resulted from deficient DNA damage response contributes to the occurrence of cancer. One the other hand, these defects could also be exploited as a therapeutic opportunity, which is preferentially more deleterious in tumor cells than in normal cells. An expanding repertoire of DDR-targeting agents has rapidly expanded to inhibitors of multiple members involved in DDR pathways, including PARP, ATM, ATR, CHK1, WEE1, and DNA-PK. In this review, we sought to summarize the complex network of DNA repair machinery in cancer cells and discuss the underlying mechanism for the application of DDR inhibitors in cancer. With the past preclinical evidence and ongoing clinical trials, we also provide an overview of the history and current landscape of DDR inhibitors in cancer treatment, with special focus on the combination of DDR-targeted therapies with other cancer treatment strategies.Since nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism of NF-κB for 35 years, which lead to significant progress. Meanwhile, the molecular mechanisms regulating NF-κB activation have also been illuminated, the cascades of signaling events leading to NF-κB activity and key components of the NF-κB pathway are also identified. It has been suggested NF-κB plays an important role in human diseases, especially inflammation-related diseases. These studies make the NF-κB an attractive target for disease treatment. This review aims to summarize the knowledge of the family members of NF-κB, as well as the basic mechanisms of NF-κB signaling pathway activation. We will also review the effects of dysregulated NF-κB on inflammation, tumorigenesis, and tumor microenvironment. The progression of the translational study and drug development targeting NF-κB for inflammatory diseases and cancer treatment and the potential obstacles will be discussed. Further investigations on the precise functions of NF-κB in the physiological and pathological settings and underlying mechanisms are in the urgent need to develop drugs targeting NF-κB for inflammatory diseases and cancer treatment, with minimal side effects.Cancer metastasis is responsible for the vast majority of cancer-related deaths worldwide. In contrast to numerous discoveries that reveal the detailed mechanisms leading to the formation of the primary tumor, the biological underpinnings of the metastatic disease remain poorly understood. Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle, and grow at other parts of the body. Epithelial-mesenchymal transition and anoikis resistance of tumor cells are the main forces to promote metastasis, and multiple components in the tumor microenvironment and their complicated crosstalk with cancer cells are closely involved in distant metastasis. In addition to the three cornerstones of tumor treatment, surgery, chemotherapy, and radiotherapy, novel treatment approaches including targeted therapy and immunotherapy have been established in patients with metastatic cancer. Although the cancer survival rate has been greatly improved over the years, it is still far from satisfactory. In this review, we provided an overview of the metastasis process, summarized the cellular and molecular mechanisms involved in the dissemination and distant metastasis of cancer cells, and reviewed the important advances in interventions for cancer metastasis.The nose is the initial site of viral infection, replication, and transmission in the human body. Nasally inhaled vaccines may act as a promising alternative for COVID-19 management in addition to intramuscular vaccination. In this review, the latest developments of nasal sprays either as repurposed or antiviral formulations were presented. Nasal vaccines based on traditional medicines, such as grapefruit seed extract, algae-isolated carrageenan, and Yogurt-fermenting Lactobacillus, are promising and under active investigations. Inherent challenges that hinder effective intranasal delivery were discussed in detail, which included nasal device issues and human nose physiological complexities. We examined factors related to nasal spray administration, including the nasal angiotensin I converting enzyme 2 (ACE2) locations as the delivery target, nasal devices, medication translocation after application, delivery methods, safety issues, and other nasal delivery options. read more The effects of human factors on nasal spray efficacy, such as nasal physiology, disease-induced physiological modifications, intersubject variability, and mucociliary clearance, were also examined. Finally, the potential impact of nasal vaccines on COVID-19 management in the developing world was discussed. It is concluded that effective delivery of nasal sprays to ACE2-rich regions is urgently needed, especially in the context that new variants may become unresponsive to current vaccines and more refractory to existing therapies.Triple negative breast cancer (TNBC) cells lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). Thus, TNBC does not respond to hormone-based therapy. TNBC is also an aggressive subtype associated with poorer prognoses compared to other breast cancers. Conventional chemotherapeutics are used to manage TNBC although systemic relapse is common with limited benefits being reported as well as adverse events being documented. Here, we discuss current therapies for TNBC in the neo- and adjuvant settings, as well as recent advancements in the targeting of PD-L1-positive tumors and inclusion of PARP inhibitors for TNBC patients with BRCA mutations. The recent development of cyclin-dependent kinase (CDK) 4/6 inhibitors in ER-positive breast cancers has demonstrated significant improvements in progression free survival in patients. Here, we review preclinical data of CDK 4/6 inhibitors and describe current clinical trials assessing these in TNBC disease.Eastern countries are a major source of medicinal plants, which set up a rich source of ethnopharmacologically known medicines used in the treatment of various diseases. These traditional medicines have been known as complementary, alternative, or nonconventional therapy across globe for ages. Tuberculosis (TB) poses a huge global burden and leads to maximum number of deaths due to an infectious agent. Treatment of TB using Directly Observed Treatment Short-course (DOTS) therapy comprises multiple antibiotics is quite lengthy and causes serious side-effects in different organs. The length of the TB treatment leads to withdrawal from the patients, which paves the way for the emergence of drug resistance in the bacterial population. These concerns related to therapy need serious and immediate interventions. Traditional medicines using phytochemicals has shown to provide tremendous potential in TB treatment, mainly in the eradication of Mycobacterium tuberculosis (M.tb), increasing natural immunity, and managing the side effects of anti-TB drugs. This review describes the antituberculosis potential of selected ethnopharmacologically important phytochemicals as potential immune-modulator and as an adjunct-therapy in TB. This review will be a useful reference for researchers working on ethnopharmacology and will open the door for the discovery of novel agents as an adjunct-therapy to tuberculosis.Gender-based violence (GBV), specifically violence against women, is a worldwide pandemic. Prevalence is further escalated in low-and-middle-income countries and in humanitarian crises. Survivors are left with a combination of post-traumatic stress disorder, depression and anxiety. These mental health disorders lead to further morbidity and mortality. Despite its high prevalence and co-morbidities, gender disparities and mental health stigma globally lead to few interventions developed for this population. The aim of this review is to highlight the mental health interventions developed in the past 5 years, for women following GBV in low-and-middle-income countries. It aims to discuss their efficacy and controversies when implemented into healthcare systems, understand the gaps that remain in the field and suggest future research developments. A thorough literature search revealed 16 new interventions available for improving mental health outcomes for women following GBV in low-and-middle-income countries. Following an in-depth evaluation of the papers, one intervention was successful in effectively implementing treatment into healthcare systems-"PM+." However, it proved only to be effective in the short term. Further research must be done for improving long-term mental health outcomes. Results demonstrated poor follow-up for women engaging in group therapy. The review also highlights community workers were used in service delivery to reduce barriers accessing care. No interventions proved effective in humanitarian crises, despite GBV escalated in these settings. There are very few interventions available in comparison to the prevalence of this global health issue. Therefore, this review encourages further research and improvements in mental healthcare interventions following GBV.