Guanidinium-based Integrated Peptide Dendrimers: Pioneer Nanocarrier in Cancer Therapy.

The landscape of cancer therapy has witnessed a paradigm shift with the emergence of innovative delivery systems, and Guanidinium-based Peptide Dendrimers have emerged as a vanguard in this transformative journey. With their unique molecular architecture and intrinsic biocompatibility, these dendrimers offer a promising avenue for the targeted delivery of therapeutic cargo in cancer treatment. This comprehensive review delves into the intricate world of Guanidinium- based Peptide Dendrimers, unraveling their structural intricacies, mechanisms of action, and advancements that have propelled them from laboratory curiosities to potential clinical champions. Exploiting the potent properties of guanidinium, these dendrimers exhibit unparalleled precision in encapsulating and transporting diverse cargo molecules, ranging from conventional chemotherapeutics to cutting-edge nucleic acids. The review navigates the depths of their design principles, investigating their prowess in traversing the complex terrain of cellular barriers for optimal cargo delivery. Moreover, it delves into emerging trends, such as personalized therapeutic approaches, multimodal imaging, and bioinformatics-driven design, highlighting their potential to redefine the future of cancer therapy. Crucially, the review addresses the pivotal concerns of biocompatibility and safety, examining cytotoxicity profiles, immune responses, and in vivo studies. It underscores the importance of aligning scientific marvels with the stringent demands of clinical applications. Through each section, the narrative underscores the promises and possibilities that Guanidinium-based Peptide Dendrimers hold and how they can potentially reshape the landscape of precision cancer therapy.

Bioinformatics Analysis to Uncover the Potential Drug Targets Responsible for Mycobacterium tuberculosis Peptidoglycan and Lysine Biosynthesis.

Drug-resistant tuberculosis (TB), which results mainly from the selection of naturally resistant strains of Mycobacterium tuberculosis (MTB) due to mismanaged treatment, poses a severe challenge to the global control of TB. Therefore, screening novel and unique drug targets against this pathogen is urgently needed. The metabolic pathways of Homo sapiens and MTB were compared using the Kyoto Encyclopedia of Genes and Genomes tool, and further, the proteins that are involved in the metabolic pathways of MTB were subtracted and proceeded to protein-protein interaction network analysis, subcellular localization, drug ability testing, and gene ontology. The study aims to identify enzymes for the unique pathways for further screening to determine the feasibility of the therapeutic targets. The qualitative characteristics of 28 proteins identified as drug target candidates were studied. The results showed that 12 were cytoplasmic, 2 were extracellular, 12 were transmembrane, and 3 were unknown. Furthermore, druggability analysis revealed 14 druggable proteins, of which 12 were novel and responsible for MTB peptidoglycan and lysine biosynthesis. The novel targets obtained in this study are used to develop antimicrobial treatments against pathogenic bacteria. Future studies should further shed light on the clinical implementation to identify antimicrobial therapies against MTB.

Quality of Life of Cancer Patients during Chemotherapy in Indonesia: A Comparison of EORTC QLQ-C30 and EQ-5D-5L, Based on Patients' Characteristics.

One of the important outcomes to define the success of cancer treatment is the health-related quality of life (HRQoL) that can be measured using generic and/or specific instruments. Our study aims to define the cancer patients' HRQoL in some hospitals in Indonesia as measured by the European Organization for Research and Treatment for Cancer (EORTC QLQ-C30) and the EQ-5D-5L, to define the differences of cancer patients' HRQoL referring to patients' characteristics, and to explore determinants of cancer patients' HRQoL. We recruited 451 cancer patients using a cross-sectional design in two referral hospitals in Central Java, Indonesia, using the purposive sampling technique. All subjects, recruited from July 2020 to October 2021, met the inclusion criteria, namely, adult patients diagnosed with cancers in all stages who willingly participated in the study. The Indonesian value set was used to obtain the EQ-5D-5L index score. We further analyzed the data based on cancer stages and compared two questionnaires using independent t test. We highlighted that most of the cancer patients are female (69.4%), young (86%), and at advanced stages of cancer (54.1%). The physical and role functions and global health status of the cancer patients are poor, and the most severe symptom is fatigue. Moreover, most of them experience severe pain and perform daily activities with difficulties. Some patients' characteristics show significant influences on the HRQoL domains in both questionnaires (p < 0.05). Interestingly, both of the questionnaires have shown significant correlations between similar domains and revealed the poor HRQoL of advanced cancer patients (p < 0.05). Our study finds that cancer patients still have poor HRQoL in some domains. We suggest to the health providers that they apply education and psychological intervention to increase their HRQoL.

Evaluation for the Genetic Association between Store-Operated Calcium Influx Pathway (STIM1 and ORAI1) and Human Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection.

Hepatocellular carcinoma (HCC) often develops from chronic hepatitis B (CHB) through replication of hepatitis B virus (HBV) infection. Calcium (Ca2+) signaling plays an essential role in HBV replication. Store-operated calcium (SOC) channels are a major pathway of Ca2+ entry into non-excitable cells such as immune cells and cancer cells. The basic components of SOC signaling include the STIM1 and ORAI1 genes. However, the roles of STIM1 and ORAI1 in HBV-mediated HCC are still unclear. Thus, long-term follow-up of HBV cohort was carried out in this study. This study recruited 3631 patients with chronic hepatitis (345 patients with HCC, 3286 patients without HCC) in a Taiwanese population. Genetic variants of the STIM1 and ORAI1 genes were detected using an Axiom CHB1 genome-wide array. Clinical associations of 40 polymorphisms were analyzed. Three of the STIM1 single-nucleotide polymorphisms (SNPs) (rs6578418, rs7116520, and rs11030472) and one SNP of ORAI1 (rs6486795) showed a trend of being associated with HCC disease (p < 0.05). However, after correction for multiple testing, none of the SNPs reached a significant level (q > 0.05); in contrast, neither STIM1 nor ORAI1 showed a significant association with HCC progression in CHB patients. Functional studies by both total internal reflection fluorescence images and transwell migration assay indicated the critical roles of SOC-mediated signaling in HCC migration. In conclusion, we reported a weak correlation between STIM1/ORAI1 polymorphisms and the risk of HCC progression in CHB patients.