International Journal of Molecular Sciences

Hair loss is a common condition that affects a large number of people worldwide, impacting both men and women. Its development is closely linked to the function of hair follicle dermal papilla cells (HFDPCs), which play a pivotal role in maintaining hair growth and follicle integrity. However, these cells are particularly vulnerable to oxidative stress generated under psychological or environmental stressful conditions. Preserving the mitochondrial function and biological activity of HFDPCs is critical for preventing stress-related hair loss. This study investigated the protective and hair growth-promoting effects of 3-hydroxypropionic acid (3-HP), a naturally occurring organic acid with antioxidant potential, on HFDPCs exposed to H₂O₂-induced oxidative stress conditions. Treatment with 3-HP significantly enhanced cell viability and migration in H₂O₂-damaged HFDPCs. In addition, 3-HP reduced intracellular reactive oxygen species (ROS) accumulation and improved mitochondrial membrane potential as well as ATP production. Furthermore, 3-HP upregulated alkaline phosphatase (ALP) expression and activated hair growth-related signaling pathways, including the Wnt/β-catenin axis. Finally, treatment with 3-HP resulted in a significant enlargement of three-dimensional spheroids in H₂O₂-damaged HFDPCs. These findings suggest that 3-HP mitigates oxidative stress-induced damage and promotes hair follicle cell function, indicating its promise as a treatment option for improving oxidative stress-related hair loss conditions.

The scorpion family Buthidae, renowned for its neurotoxin-rich venoms, dominates toxinology, while non-buthid venoms remain largely unexplored. Here, we present a comprehensive proteomic and biochemical characterization of the Amazonian chactid scorpion Brotheas amazonicus venom (BamazV), with emphasis on molecular complexity, proteolytic processing, and peptide diversity. Using an integrative venomics approach that combines molecular mass-based fractionation, reversed-phase chromatography, high-resolution mass spectrometry, N-terminal sequencing, and functional and immunological analyses, we reveal an unexpectedly complex venom profile enriched in high-molecular-weight components and extensively processed peptides, with more than 40 venom peptides sequenced by MS/MS and Edman degradation. The data provide evidence for non-canonical proteolytic events, including the generation of peptides from precursor regions not classically associated with mature venom components. In contrast to the venom of Tityus serrulatus, BamazV displays a “hydrolase-rich, neurotoxin-poor” profile, featuring a catalytically active Group III phospholipase A₂ (BamazPLA₂), a highly active hyaluronidase, metalloproteases, low-mass peptides, and potassium channel toxins. Our results suggest a hydrolytic prey-subjugation strategy, and limited cross-reactivity with commercial antivenom highlighted its distinct structural landscape. Overall, this study advances the understanding of venom evolution and proteolytic diversification in underexplored scorpion lineages, positioning B. amazonicus as a valuable model for investigating alternative venom strategies and identifying novel biotechnological scaffolds.

Endometriosis is a chronic, estrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age worldwide. It is characterized by the presence of endometrial-like tissue outside the uterine cavity, which frequently results in dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. While hormonal medications and surgical procedures are common treatments, they are often constrained by adverse effects and high recurrence rates. The aim was to systematically identify, critically appraise, and synthesize randomized controlled trials evaluating vitamin D, C, and E supplementation in women with endometriosis, focusing on their effects on pelvic pain, dysmenorrhea, dyspareunia, quality of life, oxidative and inflammatory biomarkers, and fertility-related outcomes, and to highlight methodological gaps that can inform future research and integrated therapeutic strategies. Following PRISMA guidelines, seven eligible RCTs were identified from databases including PubMed, Scopus, and ScienceDirect. The quality of these studies was assessed using the Jadad Scoring System and Cochrane RoB 2 tool. High-dose supplementation of vitamin D (50,000 IU) was found to significantly reduce pelvic pain and improve biochemical markers such as hs-CRP and total antioxidant capacity (TAC). Vitamin D appears to modulate endometrial pathways by reducing active β-catenin protein activity, which may disrupt signaling associated with lesion invasion and survival. Additionally, combined Vitamin C and E therapy (typically 1000 mg/day of Vitamin C and 800 IU/day of Vitamin E) acts synergistically to scavenge free radicals. This intervention significantly decreased oxidative stress markers, including malondialdehyde (MDA) and reactive oxygen species (ROS). Patients reported significant improvements in symptoms, including a 43% reduction in daily pelvic pain and a 37% reduction in dysmenorrhea. Despite physiological improvements, there was no statistically significant increase in pregnancy rates observed across the trials. Vitamin supplementation with D, C, and E represents a safe, low-cost adjunct therapy that can effectively mitigate endometriosis-related oxidative stress and pelvic pain. While these vitamins show promise for symptom relief, further research with larger sample sizes is required to determine their long-term impact on fertility outcomes and lesion regression.