Récentes avancées sur les peptides

Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents.

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed the management of type 2 diabetes and obesity. Gastrointestinal (GI) adverse events are the most common limitation of these therapies and a leading cause of discontinuation. Methods This narrative expert review synthesizes evidence from randomized controlled trials, observational studies, meta-analyses, and pharmacovigilance data to characterize the incidence, mechanisms, and clinical implications of GI adverse effects across approved agents and late-stage pipeline therapies. Results Nausea, vomiting, diarrhea, and constipation are established class effects, occurring in approximately 30%-50% of patients, typically during initiation and dose escalation. These events are generally mild to moderate and manageable with dose titration and dietary modification. Mechanisms include delayed gastric emptying, central activation of emetic pathways, altered intestinal motility, and physiologic effects of rapid weight loss itself. Randomized trial data are reassuring for acute pancreatitis, with no class-level excess risk demonstrated; pharmacovigilance signals are most plausibly explained by diagnostic misclassification rather than true causal risk. Cholelithiasis shows a probable class-level association, substantially mediated by weight loss rather than direct receptor signaling. Peri-procedural data show increased residual gastric volume without confirmed aspiration events. Preliminary data on late-stage pipeline agents (retatrutide, survodutide, and cagrilintide-semaglutide) suggest a similar GI adverse event profile to approved agents, though evidence remains largely limited. Conclusion GI adverse events with GLP-1-based therapies are predictable and manageable. A proactive, patient-centered approach is essential to optimize adherence, safety, and clinical outcomes as newer agents expand the therapeutic landscape.

The therapeutic potential of melatonin: Focus on the SIRT1 signaling pathway.

Melatonin (N-acetyl-5-methoxytryptamine) is a pleiotropic indoleamine involved in diverse physiological and cellular processes and has consequently been investigated in numerous disease models. This molecule is primarily produced in the pineal gland and is well-known for its diverse functions including antitumor, immunomodulatory, antioxidant, antihypertensive, and sedative effects. It is also involved in the regulation of body weight, gastrointestinal function, reproduction, thermoregulation, and cardioprotection. Melatonin exerts its protective effects by modulating various molecular pathways. Among the signaling pathways implicated in these effects, the sirtuin-1 (SIRT1) pathway has received considerable attention. SIRT1 is a well-studied member of the mammalian sirtuin family that functions as a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase. SIRT1 shuttles between the cytoplasm and the nucleus, where it deacetylates histones and other proteins. This activity impacts various cellular functions such as cell survival, metabolism, growth, aging, and stress resistance. Available evidence suggests that melatonin may modulate SIRT1 activity and thereby influence processes involved in inflammation, oxidative stress, apoptosis, and autophagy in various pathological conditions. However, evidence regarding the role of SIRT1 in the effects of melatonin remains limited In this review, we examine the pharmacological effects of melatonin across several disease models, with particular emphasis on the potential involvement of SIRT1 signaling.

Remodeling of mitochondrial dynamics by metabolic pathways couples to oncogenic growth in <i>GNAS</i> (Gα<sub>s</sub>) mutant pancreas cancer.

Maintenance of fissed mitochondria is viewed as a defining feature of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant cancers. However, regulation of this process by accompanying comutations or environmental factors is not clearly defined. Here, by analyzing a subset of pancreatic cancer lesions driven by concurrent Kras G12D and GNAS complex locus gene (GNAS R201C/H ) mutations, we found that despite the presence of mutant Kras, hyperactive Gnas R201C maintains mitochondria predominantly in a fused state, which is necessary for tumor growth. Multiplex proteomics, super-resolution microscopy, loss- and gain-of-function studies, coupled with metabolite rescue experiments, revealed that Gnas R201C -regulated branched-chain amino acid (BCAA) pathway is a previously unidentified regulator of mitochondrial morphology. Mechanistically, the BCAA pathway, the associated tricarboxylic acid cycle, and aspartate metabolism converge on nicotinamide adenine dinucleotide (NADH-NAD + ) metabolites to promote mitochondrial elongation. NAD + availability is crucial for mitochondrial fusion, as facilitating NAD + generation through alternative means promotes fusion. Collectively, we unraveled a new mechanism that drives mitochondrial fusion and showed that the combination of oncogenic signaling and metabolism can maintain distinct mitochondrial morphology within genetic subsets of KRAS-mutant pancreatic cancer.

Increasing Direct-to-Consumer Use of Semax and Selank Peptides Decoded from LLM-Curated Clinical Notes and Physician Adjudication

Semax and Selank are synthetic regulatory peptides that are not FDA-approved for human use but are marketed direct-to-consumer for cognition, mood and stress resilience. The extent of the documented use of these unapproved peptides in routine clinical care remains poorly characterized and, because neither is dispensed through regulated pathways, is largely absent from structured medication data of Electronic Health Records (EHRs). Using Large Language Model (LLM) curation of de-identified clinical notes from the nference federated data network with manual adjudication of the LLM-curated insights, here we characterize the clinically documented use of each peptide and the real-world medical contexts in which their use occurs. Clinical note documentation of both Semax and Selank increased starting in 2024, with an average quarter-over-quarter growth of 14% for Semax and 16% for Selank over the past year. Among 43 and 39 patients with clinical note-mentions of Semax or Selank, use was confirmed via LLM curation in 22 (51%) and 27 (69%) patients, respectively. Physician adjudication agreed with the LLM’s use classification in 164 of 165 individual note-level assessments (99.4%) across patients with a Semax or Selank mention, including patients whose use was not confirmed. In the pooled cohort of patients with confirmed Semax or Selank use (N = 49), cognitive enhancement (28.6%) and mood/anxiety/stress support (28.6%) were the most common reasons for use provided by the patients, with less common reasons including energy or performance, sleep, musculoskeletal and gastrointestinal indications. Manual adjudication showed 86.7% agreement with the LLM-curated reasons for use. Both peptides were commonly administered intranasally (37%), and there was documentation of “stacking” with other peptides in 33 patients (67%), such as CJC-1295, ipamorelin, semaglutide, and tirzepatide. In the pooled cohort, clinical notes recorded patient-reported positive or effective responses in 16 of 49 patients (33%) and product- or administration-related safety concerns or adverse-event sentiments in 13 of 49 (27%). Manual adjudication agreed with LLM-curated self-reported-effect classifications in 94.2% of 103 reviewed records. Manual review showed isolated dyspnea, palpitations, flushing, and emergency department visits during the temporal periods overlapping with patient-reported use of Semax or Selank (n<11). This study is not designed to evaluate the effectiveness or harm of Semax or Selank. Rather, it highlights the rising use of unapproved direct-to-consumer peptides without any structured coding mechanism in EHR systems, emphasizing the need for greater awareness among healthcare practitioners.

MOTS-c mediates remote ischemic preconditioning-induced protection against lung ischemia-reperfusion injury via NRF2-dependent mitochondrial biogenesis.

BPC 157 in Rodent Ischemia-Reperfusion Injury: A Critical Review of Preclinical Evidence.

Ischemia-reperfusion injury (IRI) is a clinically important consequence of blood-flow restoration after ischemia and contributes to tissue damage across multiple organ systems. This critical review evaluates the preclinical evidence for BPC 157 in rodent IRI and related reperfusion-associated vascular injury models, with particular attention to oxidative stress, endothelial and nitric oxide (NO)-related responses, inflammation, apoptosis, angiogenic signaling, and tissue injury. Searches were performed up to 24 June 2026 across PubMed/MEDLINE, Web of Science Core Collection, Scopus, PMC, publisher/DOI metadata, ClinicalTrials.gov, FDA materials, and WADA materials. Peer-reviewed rodent studies involving conventional organ-specific IRI or reperfusion-associated systemic injury were evaluated as the core IRI/reperfusion evidence according to the experimental model, BPC 157 dose, route and timing, measured outcomes, and methodological limitations, while selected major-vessel occlusion models were considered separately as related in vivo vascular evidence. Endothelial, vascular-ring, human ex vivo, and regulatory/clinical sources were used as contextual evidence rather than as evidence of IRI efficacy. Meta-analysis was not performed because of substantial heterogeneity in organ systems, injury paradigms, doses, routes, treatment timing, and outcome measures. Across the available rodent literature, BPC 157 administration has been associated with attenuation of oxidative injury, modulation of NO-related vascular responses, reductions in inflammatory and apoptotic markers, and changes in VEGF/VEGFR2-Akt-eNOS-related signaling. Organ-specific findings include biochemical, molecular, and histological protection in lower-extremity skeletal-muscle IRI; attenuation of distant-organ injury following limb IRI; neuronal and functional effects in hippocampal IRI; vascular and tissue-protective responses in intestinal/colonic IRI; and hemodynamic and histological effects in hepatic Pringle-maneuver IRI. However, the evidence base remains heterogeneous and frequently relies on short observation periods, single-dose paradigms, and incompletely characterized risk-of-bias domains. Reperfusion-like systemic and major-vessel occlusion models provide additional mechanistic context but should not be considered equivalent to conventional organ-specific IRI. Current evidence therefore supports BPC 157 as a hypothesis-generating investigational candidate for further preclinical IRI research rather than as an established therapy. Independent blinded replication, dose-response and therapeutic-window studies, pharmacokinetic/pharmacodynamic characterization, rigorous toxicology, and ultimately controlled human studies would be required before clinical translation could be considered.

Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.

Cardiovascular disease is strongly influenced by mitochondrial dysfunction, yet how mitochondrial stress is communicated beyond the affected cell to coordinate systemic responses remains incompletely understood. Mitokines are stress-responsive signaling factors that link mitochondrial perturbation to cellular and interorgan adaptation. These include nuclear-encoded proteins such as fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), as well as mitochondrial-derived peptides including Humanin and MOTS-c. This review critically examines mitokine regulation and signaling in the context of cardiovascular stress, with emphasis on mitochondrial unfolded protein response and integrated stress response pathways, receptor and downstream signaling mechanisms, and the functional divergence among major mitokines. Transient mitokine responses during physiological or metabolic challenge may support metabolic flexibility, cytoprotection, and stress adaptation, whereas persistent elevations of FGF21 and GDF15 in cardiovascular and cardiometabolic disease frequently accompany unresolved mitochondrial stress and adverse clinical phenotypes. Importantly, such associations do not establish that sustained mitokine signaling is itself maladaptive, and major mechanistic uncertainties remain, particularly for mitochondrial-derived peptides. We integrate these observations within a proposed "mitokine code" framework in which mitokine identity, relative patterns, temporal dynamics, and disease context may collectively provide information about mitochondrial stress and systemic adaptation. We further evaluate the potential and current limitations of mitokines as cardiovascular biomarkers and therapeutic targets. This framework positions mitokine signaling at the interface between mitochondrial dysfunction, systemic stress adaptation, and cardiovascular disease while identifying mechanistic and translational questions requiring prospective validation.

Rising Use of Unapproved BPC-157 (“Wolverine Peptide”) and Associated Patient-Reported Outcomes Curated from Clinical Notes

Body Protection Compound-157 (BPC-157) is an unapproved synthetic peptide marketed directly to consumers despite limited human evidence on benefits and risks. We characterized the use of BPC-157 and patient-reported outcomes from 2020 through 2026 using Large Language Model (LLM) curation of de-identified clinical notes from a U.S. federated network with physician validation of each LLM-curation exercise. Of 1,536 patients with a note mentioning BPC-157, 1,039 (67.6%) had documented use, and quarterly newly confirmed users increased 33-fold between 2020 and 2026. Among 972 BPC-157 users with recorded race, 95.9% were White, compared with 78% of the background care population, representing a 1.23-fold enrichment (chi-square test across racial categories, P < 0.001). Among patients with newly documented BPC-157 use, the male proportion increased from 57% in 2020 to 70% in 2026 (Cochran–Armitage trend test across years, P < 0.001), while mean age decreased from 55 years in 2020 to 49 years in 2026. Among 205 patients with a documented consumer source (19.7% of confirmed users), BPC-157 was most commonly obtained from compounding pharmacies (36%) or gray-market peptide vendors (35%). Other therapeutic agents were co-used with BPC-157 by 525 of 1,039 users (50.5%), most commonly testosterone (17.0%), NSAIDs (14.7%), TB-500 (12.9%), and corticosteroids (11.7%), while physical therapy (15.3%), surgery (12.6%), exercise counseling (8.3%), and diet counseling (6.3%) were the documented non-drug co-interventions. Physician-adjudicated extraction accuracy was 96.0% for BPC-157 co-therapies and 74.4% for non-drug interventions, which were treated as exploratory. Reasons for use were documented for 644 patients and included pain (33% of all 1,039 users), gastrointestinal conditions including reflux, inflammatory bowel disease or gastritis (14%), prior injury (11%), and post-surgical healing (10%), physician adjudicated LLM accuracy of 83.9%. Among 80 users with ascertainable start timing, BPC-157 use preceded first clinician documentation by a mean of 60 days. Reported use averaged 2.2 months among 130 patients (12.5%) with an explicitly documented BPC-157 use duration, with 96.7% extraction accuracy. The specialties most often first documenting use were family medicine, internal medicine, gastroenterology, and orthopaedic surgery. Symptomatic improvement of pain, wound or tissue healing and functional return was documented in 79% of 354 BPC-157 users with a directional response, and symptomatic worsening in 5% of the users (LLM-extraction accuracy 78.4%). Response direction was unavailable for 685 of 1,039 users (65.9%). These reports cannot establish efficacy or distinguish BPC-157 effects from peptide stacking, other co-treatments, non-drug interventions, placebo effects or selection, reporting and confirmation biases. LLM-curated adverse events during BPC-157 use were infrequently noted and likely subject to under-reporting, with documented evidence of neuropsychiatric (1.4%), injection-site hypersensitivity (1.4%), and gastrointestinal (1.3%) events, with physician-adjudicated accuracy of 93.9% for drug-attributed adverse-events. With BPC-157 use rising rapidly despite minimal prospective studies and limited evidence-backed consumer awareness of its risk–benefit profile, this study highlights the need for facilitating structured EHR capture of broader gray-market peptide use and a continuous assessment of guidelines to better support healthcare practitioners.

Acute impact of afamelanotide on UVR erythemal and melanogenic responses in healthy humans in vivo: an exploratory study.

Afamelanotide, an analogue of α-melanocyte stimulating hormone, activates the melanocortin-1 receptor and has a range of protective properties as demonstrated largely in vitro. While afamelanotide is approved to treat a visible light-induced inflammatory dermatosis, erythropoetic protoporphyria, its acute effects in vivo are poorly characterised. We explored short-term effects of afamelanotide on the acute inflammatory response of UVR-induced erythema and on the melanogenic response, in healthy humans. Participants (n = 9, 5 M:4 F, 27-43y, phototypes II-III) had melanin density and skin lightness measured at six skin sites using spectrophotometry. A broadband UVB dose-series (7-80 mJ/cm 2 erythemally-weighted UVR, Philips TL12) was applied to buttock skin. After 24 h, minimal erythema dose (MED) was assessed, spectrophotometric measurements were taken of erythema at each dose site and two unexposed sites, and an unexposed site was biopsied. Afamelanotide was administered (16 mg subcutaneous implant) and after six days the same UVR dose-series applied to contralateral buttock skin, and measurements and biopsy repeated. Melanin was stained in biopsy sections (modified Warthin-Starry method) and quantified by image analysis. The UVR-erythema dose response (area-under-curve) decreased post-afamelanotide (mean 3.5 pre, 2.7 post, P = 0.018) with an apparent increase in MED (median 21 mJ/cm 2 pre, 29.9 post, not sign.). Melanin density (reflectance at 420 and 400 nm) increased (mean overall increase 2.4% to 2.9%, P = 0.001), while melanin staining was unaltered. The demonstrated protection against acute UVR-induced erythema shortly after afamelanotide application supports that anti-inflammatory effects observed in vitro may operate in vivo, warranting further investigation in acute UVR-induced inflammatory conditions.

GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap.

Background/Objectives : Glycyl-L-histidyl-L-lysine (GHK) and its copper(II) complex GHK-Cu have been studied for matrix remodeling, inflammation, redox regulation, angiogenesis, and tissue repair, yet the literature frequently treats GHK-Cu as a single active ingredient despite formulation-dependent variation in coordination state, speciation, stability, pharmacokinetics, and toxicity. We critically evaluate GHK-Cu simultaneously as a bioactive metallopeptide and as a drug-delivery cargo, with explicit separation of apo-GHK, canonical GHK-Cu, GHK-derived copper peptides, and non-GHK copper-peptide systems. Methods : We conducted a structured systematic evidence-mapping review of PubMed/MEDLINE, Europe PMC, major publisher platforms, ClinicalTrials.gov, backward citation chains, and official European Union, U.S., and ICH regulatory sources from database inception through 12 August 2026. Biological evidence level and chemical/formulation quality were graded independently using an author-defined two-axis framework. Delivery studies were extracted against a fixed matrix comprising formulation, claimed loading, molar copper occupancy, labile copper, species-resolved release, factorial controls, stability/manufacturability, and objective outcome. Quantitative pooling was not performed because active-entity definitions, formulations, doses, models, comparators, and endpoints were not quantitatively commensurable. Results : Preclinical data consistently support effects on matrix remodeling, epithelial repair, inflammatory/redox regulation, and angiogenesis, but the clinical evidence remains sparse and does not meet contemporary active-entity quality standards. Historical cosmetic reports are small or incompletely characterized; a 13-participant post-CO2-laser study was negative on objective endpoints, whereas a 2026 18-participant split-face eyebrow study reported positive cosmetic hair outcomes but did not define GHK-Cu speciation or local exposure. The ongoing phase 2 acute-wound study NCT07437586 remains recruiting and has no efficacy results; its registration cannot be used as evidence of clinical translation. Across delivery studies, particle size, polydispersity, encapsulation efficiency, total peptide/copper content, and bulk release are often reported, whereas molar occupancy, labile copper, and release of intact GHK-Cu versus apo-GHK/free copper are usually not resolved. Conclusions : Translation is limited less by biological plausibility than by pharmaceutical definition and evidence attribution. We define the "active pharmaceutical entity" operationally as the reproducible chemical state intended to mediate pharmacology at administration, not as an established regulatory designation or a claim that one immutable molecular species persists in biological fluids. We further propose, explicitly as an author-derived development framework rather than a consensus standard, a control strategy based on molar occupancy, route-specific labile copper specifications, orthogonal speciation, mechanism-linked potency, species-resolved release, factorial controls, route-specific safety decision thresholds, ICH-aligned stability, and GMP-scalable manufacture. Until these requirements are met and controlled clinical efficacy is demonstrated, GHK-Cu should be regarded as a promising but unproven therapeutic cargo rather than a clinically validated regenerative drug.

Peptides in Regenerative Medicine: A Comprehensive Review of Clinical Applications in Tissue Repair and Chronic Pain Management.

Purpose of review This narrative review summarizes the current evidence on regenerative peptides relevant to chronic pain management, including collagen peptides, body protection compound-157 (BPC-157), thymosin beta-4 (TB-4), thymosin beta-500 (TB-500), glycyl-L-histidyl-L-lysine copper (GHK-Cu), growth hormone-related peptides, and cibinetide (ARA-290). We review their proposed mechanisms of action, potential clinical applications, preclinical and clinical evidence, safety profiles, and regulatory status. Recent findings Chronic pain imposes a substantial global burden, yet conventional management strategies often fail to achieve durable, long-term outcomes and primarily focus on symptom control. Regenerative medicine has emerged as a promising alternative by targeting tissue repair and restoration. Among the various therapeutic approaches within regenerative medicine, peptide-based therapies have gained significant attention in recent decades, with growing evidence supporting the efficacy of these interventions. Despite their therapeutic potential, evidence regarding the role of regenerative peptides in chronic pain management remains limited. By synthesizing the available literature, this review aims to provide an evidence-based framework for understanding the potential role of these therapeutic peptides in chronic pain management. However, because most of these therapies remain unapproved by the U.S. Food and Drug Administration (FDA) and clinical evidence in humans is limited, their use should be guided by careful clinical judgment and ongoing evaluation of emerging evidence.

Peptide Supplements and Their Therapeutic Applications in Sports Medicine.

Background The peptide supplement market has experienced rapid growth due to marketing claims of enhanced performance and accelerated recovery from musculoskeletal injury. These peptides are increasingly popular with patients and athletes and are often perceived as low risk, despite the absence of efficacy or safety data for many emerging peptides. Purpose To summarize existing peer-reviewed data on 6 emerging peptides (BPC-157, thymosin beta-4 or TB-500, CJC-1295, MK-677, ipamorelin, and GHK-Cu [copper peptide]) for musculoskeletal recovery and enhancement in animal and human models. Study design Scoping review. Methods Three independent reviewers searched the PubMed database using permutations of peptide search terms (BPC-157, TB-500, CJC-1295, MK-677 [ibutamoren], ipamorelin, and GHK-Cu) combined with musculoskeletal tissue search terms (bone, fracture, muscle, tendon, ligament, meniscus, and cartilage) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Papers were independently screened by 2 reviewers, with a third serving as a tiebreaker. Papers examining these peptides for musculoskeletal treatment, tissue recovery, or performance in animal or human models were included. Results Overall, 67% of identified publications utilized preclinical animal models. In animal models, most commonly rats, each compound demonstrated unique mechanisms with promising but variable effects on tendon, muscle, bone, and ligament healing. Human clinical studies were limited to a handful of investigations, most lacking robust controls or rigorous study designs. Human data were heterogeneous and revealed modest improvements at best for metabolic bone health and degenerative knee pain. Some peptides such as MK-677 were associated with significant risks including congestive heart failure, and significant heterogeneity existed in dosing and route of administration. Conclusion Despite promising findings in animal studies, the claimed benefits of emerging peptide supplements for musculoskeletal recovery and performance remain unsubstantiated by current human trials. Documented risks include cardiovascular complications and metabolic dysfunction such as insulin resistance. Because of the lack of robust efficacy and safety data, peptide supplements should not currently be recommended as a replacement or adjunct for existing orthopaedic standard of care.

Peptides in Regenerative Medicine: Mechanisms, Evidence, and Translational Status

Regenerative medicine restores tissue structure and function by regulating the biological processes that are involved in cellular survival, proliferation, differentiation, as well as tissue remodeling. Peptide-based therapeutics have gained popularity as regenerative tools related to their ability to precisely modulate the defined signaling pathways. Peptides provide high target specificity, biological activity, and translational flexibility while also serving as endogenous signaling molecules that can influence the regenerative processes. FGF-18, TB4, GHK-Cu, MOTS-c, and tesamorelin demonstrate diverse regenerative mechanisms which include cartilage repair, wound healing, extracellular matrix remodeling, and tissue remodeling. Current evidence supports strong regenerative effects in preclinical studies, with clinical translation seen as well. Major barriers include limited bioavailability and delivery challenges. Continued advances in peptide engineering, delivery, and clinical evaluation will all be necessary to establish their long-term therapeutic role in regenerative medicine. This review evaluates peptide-based regenerative therapies by examining mechanisms of action, clinical evidence, and current translational status.

A Review of Randomized Controlled Trials for Vitiligo Therapies Published Between 2013 and 2023.

Vitiligo is a depigmentation disorder whose treatment remains a serious challenge. While it is generally accepted that topicals and phototherapy are helpful for generalized symmetric disease, randomized controlled trials (RCTs) provide the best evidence for treatment. Our objective was to identify and summarize RCTs for vitiligo from 2013 to 2023. A systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO) was performed per PRISMA guidelines. We searched CENTRAL, ClinicalTrials.gov, Embase, PubMed, and Web of Science for RCTs using keywords such as 'vitiligo' and/or 'treatment' or 'intervention.' A total of 652 studies underwent full-text review, and 151 studies met the inclusion criteria. We focused our study on RCTs using the vitiligo area scoring index (VASI) as the primary outcome measure, leading to 36 studies. We further narrowed our focus to studies that could be aggregated into the intervention categories: phototherapy and systemic combination therapy (n=10), topical and topical combination therapy (n=15), and systemic monotherapy (n=5). Treated versus control subjects showed statistically improved VASI after the following interventions were added to phototherapy: oral psoralen, oral minipulsed prednisone, implanted afamelanotide, topical ethyl vanillate, topical bimatoprost, and oral vitamins A and E. Effective topical therapies were ruxolitinib, calcipotriol and betamethasone, tacrolimus and mometasone, and microdermabrasion and tacrolimus. None of the systemic monotherapies was superior to their corresponding comparator.

Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV (TRIUMPH): a clinical trial protocol.

Background The Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV (TRIUMPH) study is a randomised controlled trial with the overall goal of examining the combined effect of exercise and the growth hormone-releasing hormone analogue tesamorelin on physical function. Methods TRIUMPH is a two-site, double-blind, randomised trial of 100 sedentary older adults (aged 50-80 years) living with HIV who are frail or at risk for frailty and have excess abdominal adiposity. Enrolled participants will be randomised to receive tesamorelin or placebo as an adjunct to a home-based semisupervised exercise programme for 24 weeks, followed by a 24-week extension phase of independent exercise. We will determine short-term and sustained effects of tesamorelin plus exercise on clinical endpoints, including physical function, muscle content and quality, quality of life, and exercise adherence at Weeks 24 and 48. We also will elucidate effects of tesamorelin plus exercise on biological endpoints, including muscle fat and mitochondrial function at Week 24. Ethics and dissemination Ethical approval for the TRIUMPH study was obtained from the Institutional Review Boards at participating sites. All participants provide written informed consent prior to enrolment. Study findings will be disseminated through peer-reviewed publications and scientific conferences and may inform future interventions to improve physical function among older adults living with HIV. Trial registration number NCT06554717.

Digitally Guided Hybrid Maxillary Expansion with Supragingival Mandibular Miniplates for Class III Correction in Late Adolescents: A Pilot Clinical Study.

Background: Management of skeletal Class III malocclusion of maxillary origin in late adolescence remains challenging, as conventional tooth-borne orthopedic approaches show reduced effectiveness at advanced stages of skeletal maturation. Minimally invasive, bone-anchored alternatives supported by digital workflows may improve clinical feasibility and patient acceptance. Objective: To describe a digitally guided clinical protocol combining a hybrid maxillary expander and supragingival mandibular miniplates, and to explore skeletal and dentoalveolar outcomes in late adolescents. Methods: This retrospective pilot clinical study included ten late adolescents (mean age 16.0 ± 1.3 years; range 13.8-17.7) in advanced skeletal maturation stages (CS4-CS6) with skeletal Class III malocclusion of maxillary origin. Treatment consisted of a hybrid maxillary expander anchored to palatal miniscrews and custom supragingival mandibular miniplates, placed using a fully digital workflow. Maxillary protraction was performed using a modified Alt-RAMEC protocol followed by continuous intermaxillary elastic traction for 12 months. Pre- and post-treatment cephalometric analyses were conducted. Results: A significant increase in SNA was observed (mean +6.1°, p p = 0.007), and the SeMax increased by 2.9 mm ( p = 0.0013). No significant changes were found in the SNB or mandibular plane angle. Dentoalveolar effects were limited. Conclusions: Within the limitations of this pilot clinical study, the proposed digitally guided protocol demonstrated clinically relevant maxillary advancement with minimal dentoalveolar side effects and preserved vertical control. This relatively minimally invasive approach compared to conventional subgingival miniplates and orthognathic surgery may represent a feasible treatment option for selected late adolescent patients. Further controlled studies are required to confirm these findings.

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.

Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.