Search Results (19,507)

Keloid is a benign skin disease with excessive growth of fibroblasts, characterized by too much abnormal extracellular matrix deposited in the dermis. It is generally believed that transforming growth factor-β (TGF-β) is the core cytokine that causes keloid. Previously, it was thought that its pathogenic effect was mainly attributed to the classical Smad-dependent pathway. It directly shuttles signals to the nucleus to trigger pro-fibrotic gene transcription. However, accumulating evidence now points to the equally vital role of Smad-independent signaling. Unlike the direct nuclear translocation of Smads, these alternative pathways transmit signals through rapid intracellular kinase cascades. They jointly direct the proliferation, migration, anti-apoptosis, fibrogenesis, and chronic inflammation of fibroblasts in keloids. This review attempts to comprehensively clarify the molecular processes regulated by TGF-β through non-Smad pathways (such as MAPK, PI3K/Akt, Rho GTPase, Wnt/β-catenin, JAK/STAT). Translating these non-Smad insights helps to overcome the high recurrence rates of traditional therapies. Targeting these specific molecular hubs through combination and precision therapies serves to reprogram the fibrotic microenvironment. Full article

Background: Aquatic therapy is increasingly used in post-stroke rehabilitation, but its effects on balance and gait in the chronic phase remain variably reported. This systematic review aimed to evaluate the effects of aquatic therapy, alone or combined with land-based rehabilitation, on balance and gait in individuals with chronic stroke. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted between February and March 2026. Randomized controlled trials enrolling adults with chronic stroke and evaluating aquatic-containing interventions with quantitative balance and/or gait outcomes were included. Owing to clinical and methodological heterogeneity, the primary synthesis was narrative. An exploratory random-effects meta-analysis was additionally performed for post-intervention Berg Balance Scale (BBS) scores. Results: Thirteen randomized controlled trials involving 468 participants were included. Overall, aquatic therapy was associated with more consistent improvements in balance than in gait, while combined aquatic and land-based programs generally showed broader functional gains than land-based rehabilitation alone. In the exploratory meta-analysis, the primary pooled analysis of four studies favored aquatic-containing interventions for post-intervention BBS scores (MD = 3.69, 95% CI 2.69 to 4.69; p < 0.001), with no observed heterogeneity (I² = 0%). Conclusions: Aquatic therapy may be a useful adjunctive rehabilitation strategy for improving balance in chronic stroke, whereas effects on gait appear more variable. These findings should be interpreted cautiously because the quantitative synthesis was exploratory and the overall evidence base remains heterogeneous and limited by small sample sizes and short follow-up. Full article

Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy. Full article

Background: Gastric cancer (GC) is characterized by aggressive invasion and early peritoneal dissemination, which are strongly driven by chronic inflammation and epithelial–mesenchymal transition (EMT). c-Jun N-terminal kinase (JNK), a stress-responsive serine/threonine kinase within the mitogen-activated protein kinase (MAPK) family, integrates inflammatory cues to promote EMT and metastasis. Huangjin Shuangshen granules (HJSS) is a multi-component traditional Chinese medicine (TCM) formula derived from Simiao Yong’an Decoction and clinically used as an adjuvant therapy for GC. However, whether HJSS restrains inflammation-driven metastasis through modulation of JNK-associated EMT signaling remains unclear. Methods: The anti-metastatic efficacy of HJSS was evaluated using integrated in vivo and in vitro models, combined with transcriptomics, network pharmacology and molecular validation. Results: HJSS markedly attenuated LPS-induced metastatic behavior and inflammatory activation. Multilevel analyses converged on MAPK8/JNK as a central regulatory node. HJSS reversed EMT progression and inhibited nuclear phosphorylation of JNK without affecting its upstream kinases. Thermal-shift assays and molecular docking supported potential target engagement of HJSS-derived constituents, including possible interactions with JNK-related signaling targets. Pharmacologic reactivation of JNK partially abrogated the inhibitory effects of HJSS, confirming JNK-dependent action. Conclusions: HJSS suppresses inflammation-driven GC metastasis primarily by attenuating JNK-associated EMT, potentially through modulation of JNK activation by its bioactive constituents. These findings provide mechanistic insight into HJSS as a low-toxicity anti-metastatic strategy and support further exploration of its active constituents. Full article

Background/Objectives: Myocardial ischemia–reperfusion injury (MIRI) remains an ever-growing threat in the field of cardiology, as it has become a major risk factor for unfavorable outcomes following reperfusion therapies. Oxidative stress and inflammation remain the key pathophysiological mechanisms underlying MIRI, and the presently available treatments fail to prevent this process effectively. This systematic review aimed to summarize and critically assess the latest preclinical research (2020–2026) on nanocarrier-based interventions targeting oxidative stress in MIRI, highlighting the potential of the new nanostructures in cardioprotection. Methods: A total of 24 studies meeting the PRISMA criteria have been found through a literature search of PubMed, Embase, and Web of Science databases published between 2020 and 2026. The studies eligible for inclusion had focused on the efficacy of nanocarrier-based interventions in preclinical studies of MIRI. Results: Of the 24 included studies, all investigated nanocarrier-based interventions in preclinical models of MIRI. In vitro, ex vivo, and in vivo models were diverse, with most studies being a combination of both in vitro and in vivo models. Commonly studied were lipid-based nanocarriers, polymeric nanoparticles, and biomimetic nanocarriers. Across studies assessed for this review, treatments with nanocarriers were seen to suppress inflammatory and oxidative stress pathways, with a few studies showing a suppression of cardiomyocyte apoptosis. Cardiac function was restored as determined by echocardiography analyses or ex vivo models of the myocardium, thus validating that the nanocarrier-mediated therapies are effective against MIRI. Conclusions: The analyzed preclinical studies indicate that the described therapies could provide a promising basis for future clinical trials in the treatment of MIRI, provided their safety and efficacy are confirmed in clinical trials. Full article

This research aimed to develop glycerol–gelatin vaginal suppositories loaded with melatonin to enhance the localized effects of antineoplastic agents. The solubility of melatonin in different solvents was determined, and glycofurol, which is approved for pharmaceutical use, presented the highest solubilizing capacity. Furthermore, the cytotoxicity of melatonin incorporated into suppositories against HeLa cells was evaluated using MTT assays, individually and in combination with cisplatin. The results indicate that melatonin enhances the cytotoxic effects of cisplatin. The optimal formulation obtained from an experimental design was 33% gelatin, 1% PVA, 1% PEG 6000, 10% glycerol, 15% glycofurol, and 40% water. To ensure that the vaginal suppositories presented the necessary physical properties for optimal handling and application, tests were performed to determine weight uniformity, texture, surface features and disintegration time. Vaginal suppositories weighted around 1.43 g, showed Young’s modulus values of 7389.6 N/m² and hardness around 1100 g_f, and they disintegrated after 30 min at pH 4.2. Additionally, for in vitro melatonin release, FTIR and XRD tests confirmed the presence of melatonin in the formulation. It is concluded that the developed vaginal suppositories can be explored as potential vehicles for localized delivery of melatonin to the tumor site to enhance therapeutic outcomes. Full article

Postsecondary institutions are seeing an increased prevalence of student mental health concerns and disabilities, highlighting the need for campus-based approaches that support student well-being. While college campuses provide many services to support students, occupational therapists are largely absent from these support systems, despite growing interest in this emerging field of practice. This program description and implementation case study examines preliminary indicators of feasibility for the WILL Thrive program, which delivered occupational therapy (OT) services on a college campus through a Level II fieldwork placement. Feasibility was examined across domains of acceptability, demand and implementation using an integrated approach combining a needs assessment, service development and process evaluation. Data sources included environmental observations, surveys, stakeholder interviews and process evaluation measures, including service delivery tracking, referral patterns, and resource utilization. Referrals and service utilization in this case were most frequently observed among students reporting neurodevelopmental and mental health-related functional challenges, providing preliminary indicators of potential service users, though a small, heterogeneous sample size limits generalizability. Referral patterns and engagement from the wellness center and accessibility staff highlight preliminary strengths of the program, including early indicators of acceptability and demand. In contrast, implementation barriers were also identified, including limited campus-wide understanding of the OT scope and role and constraints in on-campus OT supervision. Findings offer early, exploratory signals of feasibility for integrating OT services through an OT fieldwork II model and suggest that OT may complement existing campus supports by addressing participation-focused, functionally orientated needs. Results should be viewed as preliminary and inform future implementation studies that include systematic outcome measures, comparative analysis with existing services, and broader assessment across diverse higher education contexts. Full article

Background/Objectives: Stroke is a sudden neurological event caused by disrupted cerebral blood flow and represents a leading cause of acquired disability worldwide. Motor impairments and spasticity are among the most prevalent sequelae, significantly limiting functional independence and quality of life. Non-invasive electrotherapy has emerged as a complementary strategy in neurorehabilitation aimed at enhancing neuroplasticity and improving motor recovery. To systematically review current evidence regarding the effectiveness of non-invasive electrotherapy modalities in the rehabilitation of motor sequelae and spasticity following stroke, and to examine their theoretical and clinical rationale. Methods: A systematic literature review was conducted in accordance with PRISMA 2020 guidelines. The protocol was prospectively registered in the Open Science Framework (OSF). A comprehensive search was performed in Pubmed, Web of Science (WoS), and Scopus for studies published up to 14 November 2023, using the terms “Electric Stimulation Therapy” and “Stroke”. The methodological quality was assessed using the PEDro scale. The levels of evidence were classified according to the Oxford Centre for Evidence-Based Medicine criteria, and the risk of bias was evaluated using the Cochrane Risk of Bias tool (RoB 2). Results: Sixteen studies were included in the review. The analyzed interventions comprised neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), functional electrical stimulation (FES), neuromuscular electrical stimulation combined with transcranial magnetic stimulation (NMES + rTMS), transcranial direct current stimulation (tDCS), and afferent electrical stimulation (AES). Overall, the methodological quality of the included studies ranged from moderate to high, with PEDro scores between 6 and 9 out of 10. According to the Oxford Centre for Evidence-Based Medicine classification, most studies corresponded to level 1b evidence, while a smaller proportion were classified as level 2b. A risk of bias assessment using the Cochrane RoB 2 tool showed that the majority of the included studies presented a low risk of bias across most domains, although some concerns were identified in the domains of randomization and measurement in a limited number of trials. Across modalities, consistency within group improvement in motor function and spasticity was reported. However, between group comparisons with conventional rehabilitation were often inconsistent and did not consistently demonstrate superiority. The variability in stimulation parameters, intervention duration, and outcome measures further limited direct comparisons across studies. Conclusions: Non-invasive electrotherapy appears to be a safe and promising adjunct to conventional stroke rehabilitation. Nevertheless, further high-quality studies are required to clarify the underlying neurophysiological mechanisms and to establish standardized treatment protocols. Full article

Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) remain limited. This study aimed to evaluate whether SGLT2i combined with low-dose conventional triple therapy is non-inferior to high-dose conventional triple therapy in preventing adverse cardiovascular outcomes. Materials and Methods: This retrospective observational study included 334 patients with HFrEF treated between 31 March 2018 and 31 March 2024. Of these, 110 received SGLT2i plus low-dose conventional triple therapy, and 224 received high-dose conventional triple therapy. A non-inferiority framework was applied to compare outcomes between groups. The primary endpoint was a composite of CV death and HFH, while secondary endpoints included the individual components. Results: The composite endpoint occurred more frequently in the SGLT2i plus low-dose group. After inverse probability of treatment weighting and multivariable Cox analysis, this group demonstrated a significantly higher risk of the composite outcome (adjusted HR 4.10, 95% CI 2.07–8.13; p < 0.001). CV death was similar between groups; however, HFH was significantly more frequent in the SGLT2i plus low-dose group. Conclusions: In patients with HFrEF, SGLT2i combined with low-dose conventional triple therapy did not demonstrate comparable clinical outcomes to high-dose conventional triple therapy in reducing CV death and HFH, particularly in patients with a higher baseline burden of disease severity. These findings underscore the importance of optimizing background GDMT dosing alongside the incorporation of SGLT2i into clinical practice. Full article

Background/Objectives: Wound infections cause significant morbidity, yet current diagnostics rely on time-consuming microbial culture. Volatile organic compounds (VOCs) from bacterial metabolism offer potential for early diagnosis. This study aimed to validate the volatile metabolites profiled by gas chromatography–ion mobility spectrometry (GC-IMS) combined with machine learning for rapid identification of wound infections and certain bacterial infections. Methods: Headspace of clinical wound samples were analyzed using GC-IMS. Volatile metabolite profiles were compared between infected and non-infected groups and between Escherichia coli (E. coli)-positive and negative samples. Partial least squares discriminant analysis (PLS-DA) and Mann–Whitney U test were used for preliminary screening with variable importance in projection (VIP) > 1 and p-value < 0.05. Three machine learning algorithms, namely support vector machine (SVM), logistic regression (LR), and random forest (RF), were trained on the selected features for classification, using 5-fold cross-validation with 10 repeated runs. Model performance was assessed using key evaluation metrics, including accuracy, sensitivity, specificity, the area under the curve (AUC) and feature importance ranking to identify the most relevant biomarkers. Results: A total of 19 volatile metabolites associated with clinical wound samples were identified. The RF model achieved 90.15% sensitivity and 0.91 AUC for bacterial infection detection. For E. coli identification, LR reached 85.35% sensitivity and 0.89 AUC. Potential volatile metabolic biomarkers including elevated 3-methyl-1-butanol, 2-methyl-1-butanol, and ethyl hexanoate for identifying bacterial infection were selected through the cross-validation results of the three algorithms. Conclusions: Untargeted metabolomics by GC-IMS effectively captures infection-specific volatile metabolic signatures in complex wound samples. Integration with machine learning enables rapid, high-accuracy diagnosis of bacterial infections and E. coli identification at point of care. This approach addresses clinical metabolomics translational challenges by providing a portable and cost-effective method, potentially reducing antibiotic misuse through more timely and targeted therapy. Full article

Background: Cardiac resynchronization therapy (CRT) improves outcomes in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) and a wide QRS complex. However, up to 30–50% of patients fail to respond. The QRS Index, which quantifies QRS shortening after CRT, has emerged as a potential predictor of response. We aimed to perform a systematic review and meta-analysis to evaluate the association between QRS Index and CRT response. Methods: We searched PubMed, Scopus and Cochrane for studies reporting QRS Index values in CRT responders and non-responders. Studies defining response based on clinical, echocardiographic, or combined criteria were included. Heterogeneity was assessed using the I² statistic, and a random-effects model was applied. A meta-regression analysis explored the relationship between baseline echocardiographic parameters and QRS Index. Results: Nine studies with 1274 patients met the inclusion criteria, with 760 (59%) classified as responders and 514 (41%) as non-responders. The weighted mean ± standard deviation was 16.14 ± 13.19 in responders and 7.22 ± 14.96 in non-responders. The QRS Index was significantly higher in the responder group compared to non-responders (mean difference: 8.76; 95% CI: 6.45–11.06; I² = 45%; p < 0.00001). Meta-regression revealed that lower left ventricular end-systolic volume (LVESV) values were associated with even higher QRS Index in responders compared to non-responders (β = −0.0483; 95% CI: −0.0938; −0.0029, p = 0.0372). Conclusions: QRS Index is significantly higher in CRT responders, supporting its role as a predictor of response. Further studies are needed to standardize its clinical use and assess its prognostic impact. Full article

Introduction: Non-muscle-invasive bladder cancer (NMIBC) represents approximately 78% of newly diagnosed bladder cancers and is characterized by high recurrence rates and variable progression risk. While transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains standard management, optimal treatment of high-risk and Bacillus Calmette-Guerin (BCG)-unresponsive disease remains controversial. Radiotherapy (RT), particularly in combination with chemotherapy, has been explored as a bladder-preserving alternative. Material and Methods: We conducted a narrative review of published literature evaluating the role of definitive RT in high-risk NMIBC, with emphasis on T1 disease. Retrospective series, prospective trials, meta-analyses, and contemporary guideline recommendations were examined. For each included study, we extracted data on the extent of TURBT (maximal vs. incomplete/non-specified), use and type of concurrent chemotherapy, radiotherapy technique (3D-conformal, IMRT, or proton), treatment volume (bladder only vs. whole pelvis), and dose/fractionation schedule. Results: Early studies evaluating RT alone demonstrated modest complete response rates. More recent approaches incorporating maximal TURBT followed by concurrent chemoradiotherapy report improved outcomes, with complete response rates of approximately 80–88% and 5-year overall survival comparable to surgical series. The phase II NRG/RTOG 0926 trial in recurrent high-risk T1 disease after intravesical therapy failure demonstrated an 81% complete response rate and favorable bladder preservation outcomes. Meta-analytic data suggest 5-year recurrence-free survival around 54% and overall survival near 70%, although evidence remains limited and largely non-randomized. Advances in image-guided and hypofractionated RT may further improve therapeutic outcomes while limiting toxicity. Conclusions: while definitive chemoradiotherapy is a promising option for selected patients, it remains investigational and should be considered only in those who are unfit for or decline radical cystectomy. Prospective randomized studies are needed to better define its role in contemporary management. Full article

Accurate brain tumor segmentation in magnetic resonance imaging (MRI) is essential for diagnosis, treatment planning, and therapy monitoring. Conventional deep learning models often struggle with large variations in tumor shape, size, and contrast, as well as severe foreground–background imbalance. To address these challenges, this study presents Deep-MiSR, an enhanced encoder–decoder framework built upon DeepLabV3+ with a MobileNetV2 backbone, tailored for single-modality contrast-enhanced T1-weighted (T1CE) MRI segmentation. Three complementary components are integrated into the architecture: mixed depthwise convolution (MixConv) with heterogeneous kernels within the atrous spatial pyramid pooling module for multi-scale feature aggregation, a squeeze-and-excitation block for adaptive channel recalibration, and R-Drop regularization that enforces prediction consistency via symmetric Kullback–Leibler divergence. The model was evaluated on 3064 T1CE slices from 233 patients drawn from the publicly available Nanfang Hospital brain MRI dataset. Deep-MiSR achieved a Dice similarity coefficient of 0.9281, a mean intersection-over-union of 0.8738, a precision of 0.8839, and a 95th-percentile Hausdorff distance of 7.69 mm, demonstrating consistent improvements over both the DeepLabV3+ baseline and all prior methods evaluated on the same data. Ablation studies confirmed that each component contributes independently, with R-Drop providing the largest individual gain. These findings demonstrate that combining multi-scale convolution, channel attention, and consistency regularization constitutes an effective and computationally practical strategy for robust single-modality brain tumor segmentation. Full article

The increasing prevalence of antimicrobial resistance, together with recurring infectious disease outbreaks, has intensified the need for alternative strategies to control microbial infections beyond conventional antibiotic therapies. Antimicrobial photodynamic therapy has emerged as a promising non-antibiotic approach in which light-activated photosensitising compounds generate reactive oxygen species that induce oxidative damage to microbial cells. Plant-derived photosensitisers have attracted increasing attention due to their structural diversity, biocompatibility, natural abundance, and potential for sustainability. Natural compounds such as curcumin, hypericin, chlorophyll derivatives, flavonoids, anthraquinones, and riboflavin exhibit favourable photochemical properties that enable efficient production of reactive oxygen species upon irradiation with visible light. Through radical- and singlet-oxygen-mediated photochemical pathways, these molecules exhibit broad-spectrum antimicrobial activity against bacteria, fungi, viruses, and biofilm-associated microorganisms. This review examines the photophysical properties and mechanisms of reactive oxygen species generation associated with plant-derived photosensitisers, together with key factors influencing their antimicrobial performance. Recent advances in nanocarrier-based delivery systems, dual-wavelength activation strategies, and synergistic combination therapies are also discussed for their potential to improve photostability, enhance reactive oxygen species generation, and increase microbial inactivation efficiency. Finally, current progress, challenges, and future research directions for advancing plant-derived photosensitisers in antimicrobial photodynamic therapy are discussed. Full article

Background: Dermatology and aesthetic medicine make extensive use of microneedling, a minimally invasive and safe treatment. Across the research, it has been shown that microneedling combined with chemical peels is also more effective than chemical peels alone. However, data on procedures in dark-skinned individuals is rather scarce. Aim/Objective: This study aimed to determine the efficacy of using a 4% retinol solution product containing novel TGF-β activators and antioxidants combined with a microneedling technique in the treatment of hyperpigmentation, atrophic acne scars, and enlarged pores in patients with skin of color, generally corresponding to Fitzpatrick skin phototypes IV–VI. Methods: Each of the 10 patients underwent three peel treatment series, with a 30-day interval between each session. Moreover, skin hydration, elasticity, and pigmentation were examined using the Multi Skin Test MC 1000 Courage + Khazaka, and the Observ 520x device. Results: All patients reported an overall improvement and an enhancement in skin tone after the procedure. The majority of them stated subjective improvement in the reduction of facial skin issues: redness, hyperpigmentation, uneven structure, wrinkles, dehydration, dryness, and sebaceous gland activity. The least improvement was noted in scar reduction or liquidation. An objective evaluation revealed a statistically significant improvement in hyperpigmentation and elasticity in the study group. An improvement, however, not statistically significant, in hydration parameters was demonstrated during the study. Conclusions: This study suggests that a combined peel therapy of 4% retinol serum product containing novel TGF-β activators and antioxidants, together with a microneedling technique, may improve facial hyperpigmentation of the skin, as well as regulate sebaceous gland activity, their size, and reduce sebum production. The recommended method is relatively simple to use, low-cost, has minimal adverse effects, and is well tolerated by patients with skin of color. Full article