bims-ripira 2026-05-10 papers

bims-ripira

Biomed News

on RRM2B MDMD in Adults

Issue of 2026–05–10
fourteen papers selected by
Martín Lopo

Early Sepsis Diagnosis as a Global Imperative: The Role of Raman Spectroscopy.
The Role of Phospho-ubiquitin in Mitochondrial Health and Diseases.
Azoxystrobin induces mitochondrial dysfunction and mitochondrial pathway apoptosis by targeting the Prx1 Trp87 and Thr90 sites in oral leukoplakia.
Review of Therapeutic Potential of Coenzyme Q10 in Ophthalmology: Focus on Age-Related Macular Degeneration, Glaucoma, and Retinitis Pigmentosa.
Cryptic DNA sequences encode a temperature sensor to regulate mitochondrial suicide during neuronal differentiation.
YOD1 Regulates Neuronal Mitochondrial Unfolded Protein Response Activation by Deubiquitinating DNAJA1 After Subarachnoid Hemorrhage.
Drp1 regulates mitochondrial health and controls skeletal muscle mass through the Erk1/2-Nur77 pathway.
Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.
Mitochondrial complex III deficiency nuclear type 2: a case report and analysis of clinical onset age-related phenotypic features.
Enrichment of Rare Variants in Nuclear-Encoded Mitochondrial Metabolism Genes in Patients with Early-Onset or Familial Parkinson's Disease.
DGUOK-related mitochondrial DNA depletion syndrome presenting with neonatal cholestasis without marked hyperlactatemia: A diagnostic pitfall.
Growth Differentiation Factor-15 Could Predict Decreased Hemoglobin in Tuberculosis Treated With Linezolid-Containing Regimen.
From "Passive Supplementation" to "Active Repair": Melatonin Reshapes the Treatment Paradigm for Late-Onset Hypogonadism by Targeting Leydig Cell Senescence.
Serum GDF-15 Levels Correlate With Motor and Nonmotor Symptom Domains and Overall Disease Severity in Patients With Parkinson's Disease.

J Clin Med. 2026 Apr 20. pii: 3138. [Epub ahead of print]15(8):

Early Sepsis Diagnosis as a Global Imperative: The Role of Raman Spectroscopy.

Andrea Piccioni, Fabio Spagnuolo, Marina Sebastiani, Alberto Valentini, Giuseppe Pezzotti, Marcello Candelli, Marcello Covino, Marco De Spirito, Antonio Gasbarrini, Francesco Franceschi.

  Background/Objectives: Sepsis is a leading cause of hospital mortality and represents a time-sensitive medical emergency. Current diagnostic strategies rely on clinical assessment, severity scores, biomarkers, and blood cultures. However, blood cultures require 24-72 h for pathogen identification and demonstrate limited sensitivity, while biomarkers such as procalcitonin and C-reactive protein lack optimal specificity. These limitations support the widespread empirical use of broad-spectrum antibiotics and highlight the need for rapid, sensitive, and culture-independent diagnostic tools. Methods: A narrative literature review was conducted using PubMed and Google Scholar, including 28 studies published over the past 10 years, encompassing observational and preclinical investigations. Current evidence on the application of Raman spectroscopy in sepsis was summarized, with a dual focus on pathogen identification and the assessment of the host response. Results: Raman spectroscopy has demonstrated the ability to detect early molecular alterations in circulating immune cells and mitochondrial redox status, potentially preceding conventional biomarkers. For pathogen identification, Raman techniques have achieved diagnostic accuracies comparable to automated systems, but with significantly shorter turnaround times. Integration with microfluidics, optical tweezers, and deep learning algorithms has further enhanced performance, although these applications remain largely experimental. Conclusions: Despite these promising results, the lack of methodological standardization, spectral overlap among phylogenetically related species, limited large-scale validation, and challenges in interpreting certain spectral signatures remain unresolved. Most available evidence originates from preclinical, single-center, and controlled studies, underscoring the need for prospective multicenter trials and harmonized protocols.

Keywords:  Raman spectroscopy; blood culture; diagnosis; immunity; infection; pathogens; sepsis

DOI:  https://doi.org/10.3390/jcm15083138
J Biol Chem. 2026 May 06. pii: S0021-9258(26)02000-4. [Epub ahead of print] 113128

The Role of Phospho-ubiquitin in Mitochondrial Health and Diseases.

Kumar Suresh, Christopher Rainvillee, David E Sterner, Matthew S Goldberg, Tauseef R Butt.

  Mitochondria play a major role in cellular health, yet their contribution to chronic diseases has been underestimated. Mitochondria are essential for all tissues, and a major source of ATP in high-energy-demand organs such as brain and heart being vulnerable to mitochondrial dysfunction. Failure to repair or remove damaged mitochondria contributes to aging and chronic diseases. Cells have evolved quality control mechanisms, including mitophagy to eliminate damaged mitochondria and mitobiogenesis to replenish them. The ubiquitin-proteasome system (UPS) is responsible for removing misfolded proteins, a process that is highly ATP dependent and therefore reliant on mitochondrial function. In turn, damaged mitochondria are eliminated through coordinated actions of the UPS and lysosomal degradation through mitophagy. Many neurodegenerative diseases are characterized by the presence of disease-specific protein aggregates, such as α-synuclein aggregates in Parkinson's disease and tau neurofibrillary tangles in Alzheimer's disease. These aggregates impair mitochondrial function, while dysfunctional mitochondria generate reactive oxygen species that further exacerbate proteotoxic stress, creating a pathogenic cycle. This highlights the functional interplay between mitochondria and the UPS. Recent studies have uncovered phosphorylation of ubiquitin at Serine 65 by the mitochondrial kinase PINK1 as a key signal of mitochondrial dysfunction. Phospho-Ser65-Ubiquitin (pUb) has emerged as an indicator of mitochondrial health and a potential biomarker for aging and neurodegenerative disease. However, due largely to a lack of tools, little is known about the role of pUb in cellular physiology. Here we review the current landscape of pUb biology, the phospho-ubiquitome, and its role as biomarker for mitochondrial health, and neurodegeneration.

Keywords:  (10): mitochondria; PINK1; Parkin; aging; autophagy; biomarker; mitophagy; neurodegeneration; phospho-ubiquitin; proteasome

DOI:  https://doi.org/10.1016/j.jbc.2026.113128
Front Pharmacol. 2026 ;17 1769961

Azoxystrobin induces mitochondrial dysfunction and mitochondrial pathway apoptosis by targeting the Prx1 Trp87 and Thr90 sites in oral leukoplakia.

Wenjing Li, Yajun Shen, Lingyu Li, Min Wang, Min Zhang, Xiaofei Tang.

   Introduction: Oral leukoplakia (OLK) is a prevalent oral potentially malignant disorder with limited treatment options. Our previous research showed that Azoxystrobin (AZOX) induces apoptosis and inhibits mitochondrial complex III activity. Peroxiredoxin 1 (Prx1) plays an important role in OLK progression, and preliminary evidence suggests AZOX may target Prx1 to disrupt mitochondrial function. This study aims to elucidate the precise molecular mechanism by investigating AZOX's interaction with specific Prx1 residues.
Methods: We employed AutoDock Vina for molecular docking to predict AZOX-Prx1 interactions. Using seamless cloning, Prx1-WT, Prx1-Trp87 mutant, and Prx1-Thr90 mutant variants were constructed and expressed in DOK and Leuk1 OLK cell lines. Comprehensive assessments included cell viability (Cell Counting Kit-8, CCK-8), apoptosis (flow cytometry), mitochondrial ultrastructure (transmission electron microscopy, TEM), mitochondrial ROS (mtROS) production, membrane potential (MMP), complex III activity, cellular energy metabolism (mitochondrial stress assay), and expression of mitochondrial apoptosis-related proteins (Western blot/immunofluorescence).
Results: Molecular docking revealed AZOX forms four hydrogen bonds with the Gln94, Thr90, and Thr49 residues of Prx1 and engages in π-π interaction with Trp87. AZOX treatment significantly inhibited cell proliferation and activated mitochondrial apoptosis, evidenced by increased Bax/Bcl-2 ratio and Cytochrome C (Cyto C) release, which was accompanied by comprehensive mitochondrial dysfunction including structural damage, complex III suppression, elevated mtROS, reduced MMP, and inhibited energy metabolism. Critically, both Trp87 and Thr90 mutations substantially attenuated AZOX's effects on mitochondrial integrity and apoptotic induction.
Conclusion: AZOX may bind to the Trp87 and Thr90 sites of Prx1 to inhibit mitochondrial function and energy metabolism, and induce mitochondria-mediated apoptosis, thereby suppressing the progression of OLK.

Keywords:  azoxystrobin; mitochondrial apoptotic pathway; mitochondrial function; oral leukoplakia; peroxiredoxin 1

DOI:  https://doi.org/10.3389/fphar.2026.1769961
Antioxidants (Basel). 2026 Apr 19. pii: 506. [Epub ahead of print]15(4):

Review of Therapeutic Potential of Coenzyme Q10 in Ophthalmology: Focus on Age-Related Macular Degeneration, Glaucoma, and Retinitis Pigmentosa.

Michał Wiciński, Anna Fajkiel-Madajczyk, Zuzanna Kurant, Łukasz Rzepiński, Maciej Słupski.

  Coenzyme Q10 (CoQ10), a natural antioxidant produced by the human body, has strong anti-inflammatory properties, reduces oxidative stress, and improves mitochondrial function. It is also known for its strong neuroprotective effects. With age, endogenously produced CoQ10 levels decline, contributing to the development of chronic diseases, including eye disorders. Irreversible ocular diseases that result in blindness present a significant challenge in contemporary medicine, as no fully effective cure exists; current treatments primarily aim to decelerate disease progression, manage symptoms, and preserve residual vision. Our study reviews research on the use of CoQ10 in eye diseases like age-related macular degeneration (AMD), retinitis pigmentosa (RP), and glaucoma, which can cause permanent vision loss and are linked to oxidative stress and mitochondrial dysfunction. This article explores whether CoQ10 can be a safe and effective addition to treatment for these conditions. We also outline directions for future research and explain how CoQ10 functions in the studies discussed in this review.

Keywords:  AMD; CoQ10; RP; coenzyme Q10; glaucoma; ophthalmology

DOI:  https://doi.org/10.3390/antiox15040506
Cell Commun Signal. 2026 May 02.

Cryptic DNA sequences encode a temperature sensor to regulate mitochondrial suicide during neuronal differentiation.

Filip Vujovic, Mary Simonian, Lake-Ee Quek, Kang-Yu Peng, Neil Hunter, Ramin M Farahani.

  Accumulating evidence suggests that transient mitochondrial hyperactivity shapes the early stage of neuronal differentiation although mechanistic details remain largely unknown. Here, we report a mitochondrial suicide program which is activated in response to thermal flux to terminate this early stage of mitochondrial hyperactivity. A conserved stem loop at the mitochondrial origin of replication of the light strand operates as a thermal sensor, denaturing upon enhanced thermal flux and repressing the replication of the parental heavy strand of mitochondrial DNA. This triggers a quasi-replication of mitochondrial DNA characterised by replication of only the parental light strand. The non-replicated single-stranded heavy strand is then released and operates as a natural antisense DNA which sequesters complementary mRNAs encoded by the heavy strand. Subsequent degradation of the bound mRNAs by RNase H1 completes the cycle by triggering mitochondrial transcriptional decline and ultimately mitochondrial death.

Keywords:  Mitochondrial replication; RNase H1; Single-stranded DNA; Thermal flux

DOI:  https://doi.org/10.1186/s12964-026-02914-z
Free Radic Biol Med. 2026 May 06. pii: S0891-5849(26)00742-2. [Epub ahead of print]

YOD1 Regulates Neuronal Mitochondrial Unfolded Protein Response Activation by Deubiquitinating DNAJA1 After Subarachnoid Hemorrhage.

Xi Liu, Bixi Gao, Lei Bai, Dengfeng Lu, Zhaoming Song, Zongqi Wang, Di Li, Chao Ma, Haiying Li, Zhong Wang.

   BACKGROUND: Mitochondrial dysfunction plays a critical role in early brain injury (EBI) following subarachnoid hemorrhage (SAH) and represents a promising therapeutic target.The mitochondrial unfolded protein response (UPRmt) maintains mitochondrial homeostasis and enables neurons to cope with oxidative stress. In this study, we explored UPRmt activation mediated by OTU-deubiquitinating enzyme 1 (YOD1) / DnaJ homolog subfamily A member 1 (DNAJA1) and its role in SAH.
METHODS: We isolated UPRmt positive (UPRmt+) and UPRmt negative (UPRmt-) primary neurons by flow cytometry and validated their differential tolerance to oxidative stress following SAH. We then explored the underlying causes of differential levels of UPRmt activation. By combining molecular docking, co-immunoprecipitation, and protein stability assays, we established that YOD1 regulates the deubiquitination of DNAJA1. In addition, we assessed the neuroprotective role of YOD1 after SAH in vivo and in vitro models.
RESULTS: UPRmt+ neurons exhibited reduced oxyhemoglobin (OxyHb)-induced apoptosis and mitochondrial damage compared with UPRmt- neurons. DNAJA1 was upregulated and binding to HSP70 led to a strong activation of UPRmt. DNAJA1 stability was regulated by the ubiquitin-proteasome system, and YOD1 stabilized DNAJA1 via deubiquitination. Neuron-specific YOD1 overexpression preserved mitochondrial function, reduced neuronal apoptosis in vitro and in vivo, and improved neurological outcomes in SAH.
CONCLUSION: YOD1 stabilizes DNAJA1 through deubiquitination, promoting UPRmt activation to mitigate mitochondrial dysfunction and neuronal death during EBI following SAH.

Keywords:  DNAJA1; Deubiquitination; Mitochondrial dysfunction; Oxidative stress; Subarachnoid hemorrhage; UPR(mt); YOD1

DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.05.278
Sci Adv. 2026 May 08. 12(19): eaec0795

Drp1 regulates mitochondrial health and controls skeletal muscle mass through the Erk1/2-Nur77 pathway.

Alice M Ma, Peter H Tran, Nicole L Yang, Jennifer Ngo, Hirotaka Iwasaki, Wenjuan Ren, Simone Livit, Linsey Stiles, Sarah Wang, Trinity Ho, Emma Y Yim, Noelle Morrow, Morgan M Johnson, Caroline Cleary, Kai Zou, Rachelle H Crosbie, Yuwei Jiang, Orian S Shirihai, Jonathan Wanagat, Sushil Mahata, James A Wohlschlegel, Andrea L Hevener, Zhenqi Zhou.

The maintenance of skeletal muscle mass relies on mitochondrial quality control, including balanced dynamics and mitophagy. Dynamin-related protein 1 (Drp1), a central mediator of mitochondrial fission, is essential for these processes, yet its role in muscle mass regulation remains incompletely defined. Here, we show that acute Drp1 deletion in the skeletal muscle increases Parkin-mediated mitochondrial degradation, reduces mitochondrial DNA (mtDNA) content, and leads to severe muscle atrophy. Although dual deletion of Drp1 and Parkin restores mtDNA content, muscle loss persists. Mechanistically, Drp1 loss impairs mitochondrial respiratory chain activity, suppressing extracellular signal-regulated kinase 1/2 (Erk1/2) signaling and down-regulating the nuclear receptor subfamily 4 group A member 1 (Nur77). Pharmacologic β2-adrenergic receptor activation with clenbuterol reactivated Erk1/2, restored Nur77 expression, and rescued muscle atrophy. These findings define a Drp1-Erk1/2-Nur77 signaling axis linking mitochondrial integrity to skeletal muscle mass and identify a potential therapeutic target for muscle degeneration in mitochondrial and metabolic diseases.

DOI: https://doi.org/10.1126/sciadv.aec0795
Mol Neurobiol. 2026 May 02. pii: 603. [Epub ahead of print]63(1):

Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.

Jinghan Wang, Cancan Wang, Xinyu Yuan, Jie Yan, Hongri Huang, Fujun Li, Yanqiu You, Zhongquan Qi.

  Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons, with mitochondrial dysfunction playing a critical role in its pathogenesis. As a critical organelle in eukaryotic cells, mitochondria not only serve as the central hub for energy metabolism but also play a pivotal role in regulating inflammation and cell apoptosis. However, mitochondrial damage leads to the accumulation of reactive oxygen species (ROS), oxidative stress, and abnormal aggregation of α-synuclein (α-Syn), which collectively contribute to neuronal injury and cell death. Therefore, targeting mitochondrial dysfunction has emerged as a promising therapeutic approach for PD. Exosomes, as extracellular vesicles (EVs) secreted by cells, encapsulate various substances, including proteins, nucleic acids, and lipids. Exosomes exhibit inherent targeting ability, high stability, and low immunogenicity. Additionally, the molecular contents within exosomes can regulate the biological responses of recipient cells by modulating cellular functions and signaling pathways. These characteristics of exosomes have contributed to significant achievements in the treatment of neurodegenerative diseases over the years. This review explores the latest advancements regarding the impact of stem cell-derived exosomes on mitochondrial function in PD, focuses on the regulation of mitochondrial dysfunction in recipient cells by the exosomal cargo, and presents recent evidence that suggests mitochondrial components within exosomes may facilitate cellular recovery. The aim is to provide new insights into potential therapeutic strategies for PD and to highlight directions for future research.

Keywords:  Exosomes; Extracellular vesicles; Mitochondrial autophagy; Mitochondrial damage; Oxidative stress; Parkinson’s disease

DOI:  https://doi.org/10.1007/s12035-026-05887-9
Neurol Sci. 2026 May 07. pii: 475. [Epub ahead of print]47(6):

Mitochondrial complex III deficiency nuclear type 2: a case report and analysis of clinical onset age-related phenotypic features.

Shih-Chun Lan, Yung-Yee Chang, Shu-Fang Chen, Ying-Fa Chen, Min-Yu Lan.

   CASE PRESENTATION: Mitochondrial complex III deficiency nuclear type 2 (MC3DN2) is a rare inherited neurometabolic disease. A 34-year-old male had neuropsychiatric episodes, progressive cerebellar degeneration, myopathy, polyneuropathy, and brain stem and basal ganglion lesions since childhood. Muscle biopsy revealed mitochondrial abnormalities. Two novel TTC19 pathogenic variants were detected.
LITERATURE REVIEW: To analyze phenotypic characteristics of MC3DN2 related to clinical onset age, neurological presentation and brain MRI regarding infantile and childhood-onset (ICO) and adolescent and adult-onset (AAO) disease in a cohort composed of our patient and the cases reported in the literature were compared. It revealed that, clinically, cerebellar ataxia was common in both groups, nystagmus was more frequently noted in AAO patients, and psychiatric disturbances were more common in ICO patients. Regarding MRI findings, basal ganglion lesions were more prevalent in ICO patients, and inferior olive lesions were more frequent in AAO patients.
DISCUSSION: These conspicuous phenotypic features of MC3DN2 may suggest diagnosis of this distinctive disease. The differences in clinical features and brain lesions associated with clinical onset age could provide crucial insights into the phenotypic landscape of MC3DN2.

Keywords:   TTC19 ; Cerebellar ataxia; Leigh syndrome; Mitochondrial complex III deficiency nuclear type 2; Mitochondrial disease

DOI:  https://doi.org/10.1007/s10072-026-09073-6
Genes (Basel). 2026 Apr 17. pii: 472. [Epub ahead of print]17(4):

Enrichment of Rare Variants in Nuclear-Encoded Mitochondrial Metabolism Genes in Patients with Early-Onset or Familial Parkinson's Disease.

Gaber Bergant, Vesna M van Midden, Polina Tsygankova, Dorian Laslo, Valentino Rački, Dejan Georgiev, Eliša Papić, Marija Branković, Milena Janković, Marina Svetel, Nataša Teran, Natasa Dragasević Misković, Igor Petrović, Aleš Maver, Ivana Novaković, Zvezdan Pirtošek, Martin Rakuša, Vladimira Vuletić, Borut Peterlin.

  Introduction: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, with several proposed pathogenic mechanisms. Given the established role of mitochondrial dysfunction in PD, this study seeks to investigate the enrichment of rare genetic variants tied to mitochondrial metabolism in cases of early-onset and familial PD. Methods: We performed a retrospective analysis on 248 early-onset and familial PD patients and 1622 control individuals. We assessed both pathway-level and gene-level burden of germline rare variants detected using exome sequencing in 467 nuclear genes related to mitochondrial metabolism. Results: Gene-set mutation burden analysis indicated an increased burden in genes associated with mtDNA maintenance. In addition, gene-level analysis identified a possible association between PD and rare variant burden in 14 mitochondrial metabolism-related genes under dominant or recessive inheritance models. Conclusions: Our findings support a potential contribution of rare germline variants affecting mitochondrial metabolism to the susceptibility in early-onset and familial PD.

Keywords:  Parkinson’s disease; mitochondrial metabolism; mitochondrial variants; mutation burden analysis

DOI:  https://doi.org/10.3390/genes17040472
Mol Genet Metab Rep. 2026 Jun;47 101314

DGUOK-related mitochondrial DNA depletion syndrome presenting with neonatal cholestasis without marked hyperlactatemia: A diagnostic pitfall.

Moe Li, Hideo Sasai, Hiroaki Taniguchi, Atsushi Ishida, Yuya Kuwabara, Hideki Matsumoto, Daisuke Terazawa, Tomohiro Kanayama, Tatsuhiko Miyazaki, Akira Hara, Kei Murayama.

  Mitochondrial DNA depletion syndrome (MTDPS) is a group of severe mitochondrial disorders caused by nuclear gene variants that affect mitochondrial DNA (mtDNA) replication and nucleotide synthesis. Deoxyguanosine kinase deficiency is one of the most common subtypes, typically presenting with liver dysfunction in infancy and having a poor prognosis. We report a case of MTDPS presenting with cholestasis and mild hyperlactatemia in the neonatal period, which complicated early diagnosis. Histopathological and genetic analyses established the diagnosis. The patient, a female born at 36 weeks and 1 day of gestation, weighing 2124 g, developed cholestasis, poor feeding, and failure to thrive. Hyperlactatemia was not evident at presentation but gradually increased during the clinical course. Based on suspected mitochondrial disease, mitochondrial cocktail therapy was initiated on day 64. Liver transplantation was not feasible owing to cardiac and neurological complications, and conservative treatment was continued. However, the patient died of multiple organ failure on day 89. Postmortem liver biopsy showed a markedly reduced mtDNA copy number (8.1% of control), and genetic testing revealed a homozygous c.609_610del (p.Tyr204fs) variant in the DGUOK gene (NM_080916.3), confirming the diagnosis of DGUOK-related MTDPS. This case highlights that hyperlactatemia may be absent or only mild in the early stages of MTDPS, making timely diagnosis challenging. Mitochondrial functional analysis and genetic testing should be considered early in infants with unexplained cholestasis and liver failure, regardless of the lactate levels.

Keywords:  Cholestasis; Deoxyguanosine kinase deficiency; Hepatocerebral form; Liver transplantation; Mitochondrial DNA depletion syndrome; Mitochondrial diseases

DOI:  https://doi.org/10.1016/j.ymgmr.2026.101314
Clin Respir J. 2026 May;20(5): e70195

Growth Differentiation Factor-15 Could Predict Decreased Hemoglobin in Tuberculosis Treated With Linezolid-Containing Regimen.

Amaylia Oehadian, Prayudi Santoso, Delita Prihatni, Andini Kartikasari, Ida Parwati, Diah Handayani, Thomas Handoyo, Noorwati Sutandiyo, Bachti Alisjahbana, Dick Menzies, Rovina Ruslami.

   BACKGROUND: Linezolid effectively treats rifampicin-resistant tuberculosis (RR-TB) but can cause significant hematological toxicities linked to mitochondrial dysfunction in hematopoietic stem cells. Growth differentiation factor-15 (GDF-15) has been identified as a potential biomarker of this dysfunction. This study aimed to determine whether baseline GDF-15 levels can predict myelosuppression in RR-TB patients treated with linezolid.
METHODS: The study included patients with RR-TB from three referral hospitals who were treated with a linezolid-containing regimen for at least 4 weeks. Hematological parameters and GDF-15 levels were measured at baseline as well as at the 2nd and 4th-8th weeks of treatment.
RESULTS: Ninety-seven subjects were included in this study. By the 2nd week of linezolid treatment, GDF-15 levels significantly increased from a baseline of 635.58 (407.31-1583.65) to 708.96 (378.09-2408.89)pg/ml (p = 0.003). By weeks 4-8, 65% of patients developed myelosuppression. A correlation was found between baseline GDF-15 levels and hemoglobin reduction at weeks 4-8 (r = 0.4, p < 0.001). Baseline GDF-15 levels > 950 pg/mL identified patients with more than a 25% reduction in hemoglobin (AUC 0.756, 95% CI 0.659-0.838).
CONCLUSION: Baseline GDF-15 levels were correlated with hemoglobin changes during the 4th-8th weeks of linezolid treatment. These levels can predict myelosuppression, particularly hemoglobin changes, in patients with RR-TB undergoing long-term linezolid therapy.

Keywords:  GDF‐15; RR‐TB; hemoglobin; linezolid

DOI:  https://doi.org/10.1111/crj.70195
Aging Cell. 2026 May;25(5): e70492

From "Passive Supplementation" to "Active Repair": Melatonin Reshapes the Treatment Paradigm for Late-Onset Hypogonadism by Targeting Leydig Cell Senescence.

Hui Wu, Gang Ning, Mintao Jian, Ajian Peng, Haoyu Wang, Bonan Li, Xing Zhou.

  In the context of global population aging, public health challenges due to aging are garnering significant attention. Late-onset hypogonadism (LOH) is a common age-related condition in men characterized by progressively decreasing serum testosterone levels with age, manifesting as sexual dysfunction, reduced physical vigor, and psychological or neurological abnormalities. Testosterone is synthesized primarily in testicular Leydig cells (LCs), and LC senescence during aging is key for suppressing testosterone production. This review systematically synthesizes the multidimensional molecular mechanisms underlying LC senescence. This process is driven primarily by oxidative stress (OS) and mitochondrial dysfunction and encompasses multiple interrelated layers, including epigenetic remodeling, the senescence-associated secretory phenotype (SASP), stem Leydig cell (SLC) niche degradation, and disruption of intrinsic circadian rhythms. Exogenous testosterone supplementation therapy (TST) remains the mainstay of the clinical management of LOH; however, its long-term use increasingly poses safety risks and is inherently limited to treating symptoms. Melatonin, a molecule with pleiotropic antiaging properties, including potent antioxidant effects and the ability to improve mitochondrial function, has the potential to synergistically antagonize the aforementioned multiple LC senescence pathways. By effectively mitigating LC aging and promoting endogenous testosterone synthesis, the use of melatonin could shift the treatment paradigm for LOH from "passive hormone supplementation" to "active cellular function repair". This article recapitulates preclinical and preliminary clinical evidence on the efficacy of melatonin in treating testicular or LC dysfunction, validating its therapeutic promise, and proactively identifies critical directions for future translational research, providing valuable insights for the development of novel, etiology-oriented therapeutic strategies for LOH.

Keywords:  Leydig cells; aging; late‐onset hypogonadism; melatonin; testosterone supplementation therapy

DOI:  https://doi.org/10.1111/acel.70492
Parkinsons Dis. 2026 ;2026 9949931

Serum GDF-15 Levels Correlate With Motor and Nonmotor Symptom Domains and Overall Disease Severity in Patients With Parkinson's Disease.

Noriyuki Miyaue, Hayato Yabe, Mina Yasugi, Masahiro Nagai.

   Objective: Growth differentiation factor 15 (GDF-15) has emerged as a potential biomarker for neurodegenerative diseases. Although elevated serum GDF-15 levels have been reported in Parkinson's disease (PD), their association with clinical features has not been fully characterized.
Methods: We evaluated serum GDF-15 concentrations in 40 patients with PD and analyzed their relationships with clinical measures, including motor severity (MDS-UPDRS), quality of life (PDQ-39), sleep disturbances (PDSS-2), autonomic symptoms (SCOPA-AUT), and cognitive function (MoCA-J).
Results: Higher serum GDF-15 levels were associated with older age and greater symptom burden across multiple domains. Significant relationships were observed with MDS-UPDRS Parts I-III and total scores, PDQ-39 summary index and bodily discomfort index, two different PDSS-2 domains (motor symptoms at night and PD symptoms at night), and SCOPA-AUT total and gastrointestinal dysfunction scores. After adjusting for age, the associations between serum GDF-15 levels and MDS-UPDRS Part II, Part III, and total scores remained significant. No sex-related differences were detected. A trend toward lower MoCA-J scores with increasing GDF-15 levels was observed but did not reach statistical significance.
Conclusion: Serum GDF-15 levels are linked to both motor and nonmotor aspects of PD and may reflect overall disease burden. Further longitudinal studies are needed to determine their value for disease monitoring and prognosis.

Keywords:  Growth differentiation factor 15; Parkinson’s disease; aging; motor symptoms; nonmotor symptoms

DOI:  https://doi.org/10.1155/padi/9949931