Background: The incidence of hypertension is high in people living with HIV (PLWH). High-sensitivity C-reactive protein (hsCRP), systemic inflammation response index (SIRI), and neutrophil-to-monocyte ratio (NMR) are considered economic and convenient parameters that reflect the levels of inflammation in patients. Our aim was to explore whether indirect inflammation markers are associated with hypertension in PLWH.Methods: This was a case-control study. The case group (hypertension) comprised PLWH with hypertension, and the control group (non-hypertension) comprised sex- and age-(± 3 years)-matched PLWH without hypertension. Demographic parameters, hsCRP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune- inflammation index (SII), SIRI, lymphocyte-to-monocyte ratio (LMR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), NMR, time to HIV diagnosis, antiretroviral therapy (ART) duration, recent CD4⁺ and CD8⁺ cell counts, recent CD4⁺/CD8⁺ ratio, recent HIV viral load (HIV-RNA),and recent ART regimen were obtained from the patients’ electronic medical records. A t-test or Wilcoxon rank-sum test was performed to compare differences between the two groups, and conditional logistic regression was used to analyze the risk factors of hypertension. Correlations between inflammation markers and CD4⁺ cell counts, CD8⁺ cell counts, and CD4⁺/CD8⁺ ratio were analyzed using Spearman’s correlation.Results: In the hypertension group, body mass index (BMI), hsCRP, NLR, SII, SIRI, NMR, time to HIV diagnosis, ART duration, CD4⁺ and CD8⁺ cell counts, and CD4⁺/CD8⁺ ratio, the ratio of HIV-RNA < 100 copies/mL were all higher than those in the non-hypertension group, while the PNR was lower than that in the non-hypertension group. ART duration, CD4⁺ cell counts, HIV-RNA < 100 copies/mL, hsCRP, SIRI, and NMR were positively associated with hypertensive risk in PLWH. CD8⁺ cell counts and CD4⁺/CD8⁺ ratio was negatively associated with hypertensive risk in PLWH. SIRI was negatively correlated with CD4⁺ cell counts and CD8⁺ cell counts, but positively correlated with CD4⁺/CD8⁺ ratio.Conclusions: We identified positive associations between inflammation markers hsCRP, SIRI, NMR and hypertensive risk in PLWH. Alleviating inflammation may help control or delay the occurrence of hypertension in PLWH.

N6-methyladenosine (m⁶A) modifications control multifaceted RNA metabolism and are one of the most extensively distributed modifications on the human transcriptome, including non-coding RNAs (ncRNAs). Previous concepts of ncRNAs as “junk” transcriptional products have evolved to the concept that ncRNAs are functional regulatory molecules that determine specific biological processes and cell fates. The dysregulation of m⁶A modifications and ncRNAs have been implicated in the development of human carcinogenesis. Certain types of ncRNAs have been reported to exert regulatory effects on m⁶A machinery. However, a better understanding of the relationship between m⁶A modifications and ncRNAs in cancer is still needed. This review discusses mutual interactions between m⁶A modifications and ncRNAs and their impacts on the development of human cancer. We summarize the clinical significance of m⁶A-ncRNA networks for cancer diagnosis and treatment, and we ask challenging questions that remain unanswered in this field of research. Understanding the complex coordination between m⁶A modifications and ncRNAs will be useful for guiding the development of therapeutic interventions.

Background/Objectives: Increasing evidence reveals the likely peripheral etiology of Parkinson’s disease; however, the mechanistic insight into α-Synuclein aggregation in the periphery remains unclear. This study aimed to explore the effect of abnormal expression of renalase on dopamine metabolism, toxic DOPAL generation, and subsequently, α-Synuclein aggregation. Methods: Blood pressure (BP) was monitored while changing the body position of rats; the serum level of renalase was detected by ELISA; the mRNA/protein of renalase and α-Synuclein were determined by qRT-PCR/Western blot; DOPAL was measured using HPLC; renalase distribution was explored by immunostaining; cell viability and ultrastructure were examined by TUNEL and electron microscopy, respectively. Results: The results showed that, in PD model rats, the serum level of renalase was increased time-dependently with up-regulated renalase gene/protein expression in the nodose ganglia, nucleus tractus solitarius, and heart; a reduced dopamine content was also detected by the renalase overexpression in PC12 cells. Strikingly, up-regulated renalase and orthostatic BP changes were observed before the behavioral changes in the model rats. Meanwhile, the levels of DOPAL and α-Synuclein were increased time-dependently. Intriguingly, the low molecular weight of α-Synuclein declined coordinately with the increase in the higher molecular weight of α-Synuclein. Clear ultrastructure damage at the cellular level supported the notion of molecular findings. Notably, the α-Synuclein aggregation-induced impairment of the axonal transport function predates neuronal degeneration mediated by renalase overexpression. Conclusions: Our results demonstrate that abnormal peripheral dopamine metabolism mediated by overexpressed renalase promotes the DOPAL-induced α-Synuclein and leads to baroreflex afferent neuronal degeneration and early autonomic failure.

Chromatin architecture is highly dynamic, undergoing nanoscale rearrangements throughout the cell cycle and in response to environmental cues. In this study, we employed high-resolution stochastic optical reconstruction microscopy (STORM) to visualize chromatin organization and cellular plasticity at the nanoscale in two osteosarcoma cell lines, U2OS and MG63. To promote a tumor-suppressive bone microenvironment, we applied three biophysical modalities, namely mechanical vibration, electrical stimulation, and optical pulses, each previously linked to altered tumor behavior by reprogramming cells and generating induced tumor-suppressing (iTS) cells. These stimuli enlarged nuclear size and disrupted nuclear envelope integrity, as revealed by increased surface roughness. Critically, all three modalities transiently scattered nucleosome clusters, indicating chromatin decondensation as a hallmark of iTS cell generation. iTS cells exhibited elevated expression of histone demethylases lysine demethylase 3A (KDM3A) and lysine demethylase 4 (KDM4), accompanied by reduced levels of trimethylated histone H3 lysine 9 (H3K9me3). Consistently, pharmacological agents—Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor—induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment.