Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier.

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % of all cases. It affects millions of people worldwide. AD poses a substantial economic burden on societies and healthcare systems. AD is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. As the prevalence of AD continues to increase, understanding its pathogenesis, improving diagnostic methods, and developing effective therapeutics have become paramount. This comprehensive review delves into the intricate mechanisms underlying AD, explores the current state of diagnostic techniques, and examines emerging therapeutic strategies. By revealing the complexities of AD, this review aims to contribute to the growing body of knowledge surrounding this devastating disease.

Resistance-proof antimicrobial drug discovery to combat global antimicrobial resistance threat.

Drug resistance is well-defined as a serious problem in our living world. To survive, microbes develop defense strategies against antimicrobial drugs. Drugs exhibit less or no effective results against microbes after the emergence of resistance because they are unable to cross the microbial membrane, in order to alter enzymatic systems, and/or upregulate efflux pumps, etc. Drug resistance issues can be addressed effectively if a "Resistance-Proof" or "Resistance-Resistant" antimicrobial agent is developed. This article discusses first the need for resistance-proof drugs, the imminent properties of resistance-proof drugs, current and future research progress in the discovery of resistance-proof antimicrobials, the inherent challenges, and opportunities. A molecule having imminent resistance-proof properties could target microbes efficiently, increase potency, and rule out the possibility of early resistance. This review triggers the scientific community to think about how an upsurge in drug resistance can be averted and emphasizes the discussion on the development of next-generation antimicrobials that will provide a novel effective solution to combat the global problem of drug resistance. Hence, resistance-proof drug development is not just a requirement but rather a compulsion in the drug discovery field so that resistance can be battled effectively. We discuss several properties of resistance-proof drugs which could initiate new ways of thinking about next-generation antimicrobials to resolve the drug resistance problem. This article sheds light on the issues of drug resistance and discusses solutions in terms of the resistance-proof properties of a molecule. In summary, the article is a foundation to break new ground in the development of resistance-proof therapeutics in the field of infection biology.

Thymoquinone against infectious diseases: Perspectives in recent pandemics and future therapeutics.

The recent pandemics caused by coronavirus infections have become major challenges in 21st century human health. Scientists are struggling hard to develop a complete cure for infectious diseases, for example, drugs or vaccines against these deadly infectious diseases. We have searched papers on thymoquinone (TQ) and its effects on different infectious diseases in databases like Pubmed, Web of Science, Scopus, and Google Scholar, and reviewed them in this study. To date research suggests that natural products may become a potential therapeutic option for their prodigious anti-viral or anti-microbial effects on infectious diseases. TQ, a natural phytochemical from black seeds, is known for its health-beneficial activities against several diseases, including infections. It is evident from different in vitro and in vivo studies that TQ is effective against tuberculosis, influenza, dengue, Ebola, Zika, hepatitis, malaria, HIV, and even recent pandemics caused by severe acute respiratory syndrome of coronaviruses (SARS-CoV and SARS-CoV-2). In these cases, the molecular mechanism of TQ is partly clear but mostly obscure. In this review article, we have discussed the role of TQ against different infectious diseases, including COVID-19, and also critically reviewed the future use of TQ use to fight against infectious diseases.

Role of noncoding RNAs in cholangiocarcinoma (Review).

Cholangiocarcinoma (CCA) is a malignant tumour originating from biliary epithelial cells, and is increasing in incidence. Radical surgery is the main treatment. However, the pathogenesis of CCA is unclear. Noncoding RNAs (ncRNAs) are non­protein­coding RNAs produced by genomic transcription that include microRNAs (miRNAs), circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs). They play important roles in gene expression, epigenetic modification, cell proliferation, differentiation and reproduction. ncRNAs also serve key roles in cancer development. Numerous studies have been carried out on ncRNAs, and associated publications have shown that ncRNAs are closely associated with the physiological and pathological mechanisms of CCA. The findings of these studies can provide new insights into the diagnosis, treatment and prognosis of CCA. The present review summarizes the pathophysiological mechanisms of different types of ncRNAs, including miRNAs, circRNAs and lncRNAs in CCA, and their applications in the diagnosis and treatment of CCA.

Role of non-coding RNA in pancreatic cancer.

Pancreatic cancer is a malignant disease that develops rapidly and carries a poor prognosis. Currently, surgery is the only radical treatment. Non-coding RNAs (ncRNAs) are protein-free RNAs produced by genome transcription; they play important roles in regulating gene expression, participating in epigenetic modification, cell proliferation, differentiation and reproduction. ncRNAs also play key roles in the development of cancer; microRNA (miRNA) and long non-coding RNA (lncRNA) may lead the way to new treatments for pancreatic cancer. miRNAs are short-chain ncRNAs (19-24 nt) that inhibit the degradation of protein translation or their target gene mRNAs to regulate gene expression. lncRNAs contain >200 nt of ncRNA and play important regulatory roles in a number of malignant tumors, in terms of tumor cell proliferation, apoptosis, invasion and distant metastasis. lncRNAs can be exploited for the diagnosis and treatment of pancreatic cancer and have substantial prospects for clinical application. Nevertheless, the molecular mechanism of their regulation and function, as well as the significance of other ncRNAs, such as piwi-interacting RNA, in the pathogenesis of pancreatic cancer, are largely unknown. In this review, the structures of ncRNAs with various classifications, as well as the functions and important roles of ncRNAs in the diagnosis and treatment of pancreatic cancer are reviewed.

Insights into future therapeutics for atopic dermatitis.

INTRODUCTION: Atopic Dermatitis (AD) is a common chronic inflammatory skin disorder with a constellation of symptoms. Currently, there are numerous therapies in various phases of drug development that target the pathogenesis of AD. AREAS COVERED: Our paper aims to examine small molecule therapies and other novel agents registered for clinical trial in the phase II and mainly phase III stages of development. A literature search using PubMed as well as Clinicaltrials.gov was conducted. Clinical trial evidence of these novel agents was compiled and assessed. Both topical and oral novel therapies with diverse range of mechanistic action are currently being studied, with varying success. These include phosphodiesterase-4 inhibitors, boron molecules, Janus kinase inhibitors, cannabinoid receptors agonists, kappa-opioid receptor agonists. A variety of compounds with yet undisclosed or unknown mechanisms of action are also being studied. EXPERT OPINION: Further research through extensive clinical trials will allow for more information about these targeted therapies and their potential place in the treatment algorithm of AD. Due to the success of such therapies in treating a spectrum of chronic inflammatory diseases, we remain hopeful that the successful development of targeted therapy for AD lies ahead.

The Future of Atopic Dermatitis Treatment.

In recent years, there has been a growing movement towards the use of targeted therapies in treating of atopic dermatitis (AD), parallel to that which has occurred in psoriasis. Among the systemic medications being studied are subcutaneous or intravenously administered biologic drugs targeting specific molecules such as IL4, IL13, IL17, and IgE. Non-biologic oral therapies are also being developed for AD and include small molecule drugs targeting phosphodiesterase type IV (PDE4) inhibition or Janus Kinase (JAK) inhibition. Numerous topical formulations are also being studied, with some formulations that are novel therapies that act as topical biologic or small molecule agents with mechanisms of action similar to systemic treatments. Others are being developed as skin barrier repair therapies for reduction of AD symptoms. This chapter will discuss new advances in AD treatment from medications in the initial stages of development to those nearing FDA approval.

Gut biofilm forming bacteria in inflammatory bowel disease.

Inflammatory bowel disease (IBD) symbolizes a group of intestinal disorders in which prolonged inflammation occur in the digestive tract (esophagus, large intestine, small intestine mouth, stomach). Both genetic and environmental factors (infections, stress, diet) are involved in the development of IBD. As we know that bacteria are found in the intestinal mucosa of human and clinical observations revealed bacterial biofilms associated with patients of IBD. Various factors and microbes are found to play an essential role in biofilm formation and mucosal colonization during IBD. Biofilm formation in the digestive tract is dependent on an extracellular matrix synthesized by the bacteria and it has an adverse effect on the immune response of the host. There is no satisfactory and safe treatment option for IBD. Therefore, the current research aims to disrupt biofilm in IBD and concentrates predominantly on improving the drug. Here, we review the literature on bacterial biofilm and IBD to gather new knowledge on the current understanding of biofilm formation in IBD, host immune deregulation and dysbiosis in IBD, molecular mechanism, bacteria involved in biofilm formation, current and future regimen. It is urgently required to plan new ways to control and eradicate bacteria in biofilms that will open up novel diagnostic and therapeutic avenues for IBD. This article includes the mechanism of signaling molecules with respect to the biofilm-related genes as well as the diagnostic methods and new technologies involved in the treatment of IBD.