Genetic diseases are hall marks of various diseases such as cancer, mental retardation, birth defects and neurodegenerative diseases. Identifying genomic alterations and the genes they contain will provide molecular targets for diagnosis and therapy. Clinical laboratories have increasingly adopted next generation sequencing (NGS) as a standard for the diagnosis of hereditary disorders. NGS methods can be used to detect either germline or somatic mutations. The use of PCR-based or hybridization-based enrichment strategies, clinical analysis on a single gene, multi-gene panels, or all known protein coding genes (exome sequencing) will be applied. The validity and utility of NGS-based panel testing has been demonstrated for a wide range of conditions including: hearing loss, vision loss, cardiovascular disorders, renal disorders, neurologic disorders, and cancer predispositions. Comparative Genome Hybridization (CGH) is a technique used in cytogenetic laboratories using chromosome metaphase spreads. Array CGH greatly improves the resolution of the technique by substituting metaphase spreads with genomic fragments or clones spotted in a microarray format. This method enables scanning and analysis of whole genome in a single experiment. This array CGH is easily amenable to automation and cheaper to perform. Until NGS became available array CGH is one of the most powerful toll in diagnostic test in clinical pathology. Whole Genome Amplification (WGA) method enables preparation of genomic DNA from rear and valuable samples like blood, fine needle aspirations, biopsies and archival samples. Development of novel methods for fast, sensitive and reliable RNA quantification has recently got increasing attention. Conventional methods for RNA analysis, like Northern and slot blot hybridization are in general time consuming, laborious and allow only relative quantification within a narrow concentration range. More novel methods for RNA analysis e.g. RT-PCR and real time RT-PCR are highly sensitive, but also slightly susceptible to experimental interferences. Sandwich Hybridization Assays (SHA) from crude cell samples or in connection to PCR have been extensively used in clinical diagnostics for detection of nucleic acids from bacteria, viruses, gene mutations and for cell typing. The presentation will discuss on the use of these genomics based diagnostic methods in health and disease.

Exploration in the field of epigenetics has unveiled the significance of protein arginine methyltransferases (PRMTs) in normal development and disease. Our research identified PRMT7 as a promising target for enhancing the efficacy of cancer immunotherapy in melanoma (Srour et al., 2022, Cell Reports 38(13):110582). To investigate if PRMT7 plays a role in the tumor microenvironment especially in tumor infiltrating lymphocytes (TILs), we bred PRMT7FL/FL mice with CD4-Cre mice (CKO) to generate PRMT7 deficient T cells. PRMT7 CKO mice exhibited a substantial increase in peripheral CD8+ but not CD4+ T cells. These CD8+ T cells had an enhanced T cell effector memory-like phenotype as assessed by CD44, CD62L expression. Interestingly, PRMT7 CKO mice exhibited reduced melanoma growth following subcutaneous injection of B16.F10 cells. Ex vivo stimulation of PRMT7 CKO CD8+ T cells with αCD3 and αCD28 resulted in increased proliferation compared to control CD8+ T cells. To replicate PRMT7 depletion observed in the CKO model, we developed novel VHL-ligand coupled PROTAC inhibitors targeting PRMT7. Notably, PRMT7-deficient CD8+ T cells, whether derived from CKO mice or wild-type mice treated with PRMT7 PROTACs, exhibited enhanced melanoma cytotoxic activity in vitro. Transcriptomic analysis of PRMT7-deficient CD8+ T cells revealed multiple alternative splicing defects and upregulation of the NF-kB pathway. Our findings identify a crucial function for PRMT7 in regulating the function of CD8+ T cells and further justify the need to therapeutically target PRMT7 in immune-based therapies.

Photodynamic therapy (PDT) is an approved clinical treatment with minimal invasiveness for different types of cancers. It has the advantage of high selectivity towards tumour tissue, and lack of severe and systemic complications, with the possibility of harmless repetitive applications. Its mechanism of action involves activation of a photosensitizer (PS) by an appropriate monochromatic laser beam, with long wavelength for deeper tissue penetration. Chlorophylls are photosynthetic pigments present in all organisms that convert light energy into chemical energy. The tetrapyrrolic ring structure of chlorophylls show high level of light absorption in the red region of visible light. Activation of chlorophyllin derivatives results into generation of reactive oxygen species (ROS) that cause tumour cells toxicity and subsequent tumour regression. Therefore, PDT has been used for targeting several accessible tumours. It has been also used in treatment of precancerous and cancerous dermatological diseases. In our studies, we were able to prove the distinctive role of chlorophyllin derivatives as highly efficient photosensitizers at PDT approaches. In comparison to the conventional chemotherapeutic drugs, no major alterations to the normal physiological condition have been detected. Additionally, successful PDT approaches in tumour cells killing were also achieved via liposomal delivery system of chlorophyllin derivatives at both in vitro and in vivo models. Mechanisms underlying PDT mediated tumour cells killing and in vivo tumour regression have been also investigated. Successful development of an efficient drug delivery system for improved tissue permeation has been also conducted in an established murine dermatological tumour model for possible future clinical applications.

Healthcare transformation involves the state of the entire society in terms of knowledge and expertise building, career placement, and service level. With advanced management, innovative thinking, emotional intelligence, and effective communication techniques, there is a remarkable and progressive improvement in the healthcare services provided, along with a straightforward approach to diagnosis. Health care around the world offers a high-quality life and advances. We must think, design, and implement novel approaches to educate the health workforce development, which will lead to quality achievement in patient treatment and care, including the following:
1. Teaching, Learning, and Practice.
2. Societies, System, and Structure.
3. Technology, Innovation, and Stimulation.
4. Creativity and Emotional Intelligence.
5. Effective Communication Skills.
6. Improved health care through open change.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. The roles of individual cell types in neurodegenerative pathology are being uncovered by genetic and single-cell studies. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), stroke, especially for one of the rare disorders: Wilson's disease (WD) , involving many forms of stem cells, including embryonic stem cells and induced pluripotent (iPSC) stem cells. The authors also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings, as well as Traditional Chinese Medicines and Alternative Medicines.

Cell treatment: AD

Cell treatment: PD

Cell treatment: WD rare disease

Cell treatment: Stroke

Alternative Medicine and Cell treatment.

Diabetes mellitus (DM) is a complex metabolic disease responsible of millions of deaths every year. Patients suffering from DM are confronted with severe complications such as nephropathy, retinopathy, cardiovascular ailments, and kidney failures. Unfortunately, the existing drug artillery being used for DM management suffer from multiple side-effects thereby necessitating the need to develop new potent compounds with improved pharmacological profiles.

Molecular hybridization (MH) has recently emerged as a promising technique to develop new molecular assemblies. This technique involves an amalgamation of two or more pharmacophoric entities in single molecular architecture. The resulted molecular hybrids in most cases have been reported to display superior efficacy with respect to their parent scaffolds attributed to its ability to target multiple targets or allosteric binding. Accordingly, we employed MH to prepare a variety of molecular hybrids of medicinally significant heterocyclic pharmacophoric moieties to design and synthesize novel molecular hybrids, characterized them via 1H, 13C and 2D-NMR spectroscopic techniques and tested their antdiabetic potential by inhibiting two carbohydrate-digesting enzymes (α-glucosidase and α-amylase) which are implicated in catalytic break down of complex carbohydrates into simple sugars including glucose thereby leading to a high level of glucose in the blood (hyperglycemia). For instance, a thiazolidinone-thiadiazole molecular hybrid prepared via a multicomponent reaction exhibited dual mode of inhibition with an IC50 value of 2.5mM. In silico molecule docking simulations further revealed the participation of both hydrogen bonding and hydrophobic interaction in its stabilization with the target enzymes. Similarly, the molecular hybrid of quinoline with oxadiazole exhibited superior activity to Acarbose (an antidiabetic drug) by showing selectivity towards α-glucosidase and was found to be noncompetitive binder of the enzyme based on the enzyme kinetic studies.

Diffuse Large B-cell Lymphoma (DLBCL) exhibits significant genetic heterogeneity that impacts patient responses to R-CHOP chemotherapy. While some patients respond well, others face poor outcomes due to distinct genetic subtypes affecting drug efficacy. Recognizing the necessity for personalized treatment, this in silico study aimed to investigate how genetic profiling and multi-omic approaches could enhance the identification of prognostic biomarkers and help stratify DLBCL patients for improved therapeutic responses.

A narrative review assessed existing biomarkers in DLBCL and their impact on treatment stratification. We searched the IntOGen database to find genes that are altered and linked to DLBCL, and we succeeded in examining mutation frequencies utilizing GnomAD. The Cancer Genome Interpreter was then used to identify drugs linked to DLBCL-altered genes, contextualizing pharmacological guidance based on subtype-specific vulnerabilities.

Our results demonstrate the practical application of genetic profiling of DLBCL subtypes in significantly improving treatment outcomes. Clinical trials have shown that patients who are subtyped and receive tailored pharmacological therapies have notably higher complete recovery rates and reduced relapse rates compared to non-subtyped patients within the same cohort. This evidence supports the effectiveness of treatment strategies, especially for high-risk subtypes that exhibit chemoresistance.

Our analysis revealed statistically significant variations in allele frequency for specific gene alterations across different ethnic groups, underscoring the importance of ancestry-based stratification. However, we also identified a pressing need for research that includes diverse populations, as standard therapies developed primarily from Caucasian cohorts may not be effective for non-Caucasian patients. This aspect of our research has the potential to address healthcare disparities and improve patient outcomes.