Basal cell carcinoma (BCC) is the most common skin malignancy, and surgical excision remains the first-line treatment for most lesions. However, therapeutic options for elderly patients who are unsuitable for or decline surgery are limited. Acitretin, a systemic retinoid, has shown potential antitumor effects, while topical tretinoin may enhance local therapeutic efficacy. We herein report an elderly patient with facial BCC presenting as an ulcerative lesion on the right forehead. Reflectance confocal microscopy revealed basaloid cells arranged in cord-like structures, and histopathological examination demonstrated nests of basaloid tumor cells with peripheral palisading and retraction clefts, confirming the diagnosis of nodular BCC. The patient was treated with oral acitretin in combination with topical 0.1% tretinoin cream. After 12 weeks of treatment, the ulcerative lesion showed near-complete healing with marked clinical improvement. During the treatment course, only mild adverse events, including skin dryness and cheilitis, were observed, and no significant laboratory abnormalities occurred. This case suggests that oral acitretin combined with topical 0.1% tretinoin cream may represent a feasible and well-tolerated nonsurgical option for selected elderly patients with facial BCC, and no recurrence was observed during the 4-month follow-up.
Purpose:Exosomes derived from mammalian milk are extracellular vesicular dietary agents capable of interspecies communication. Bovine milk exosomes (BMEs) are abundant natural nanovesicular resources that are enriched in bioactive components, including proteins, lipids, and microRNAs, and as such possess tremendous potential to affect cellular functions in the consumers. Although the applications of BMEs as delivery platforms for exogenous therapeutics are well known, their endogenous therapeutic potential remains relatively undiscerned. This study aimed to examine the cytoprotective role of BMEs as stand-alone therapeutic agents on human embryonic kidney (HEK293T) cells exposed to a prevalent environmental toxicant, lead (Pb). Methods:Isolation of BMEs was performed using standardized ultracentrifugation-based protocols. The physico-biochemical characterization of BMEs was performed using electron microscopy, Western blotting and dynamic light scattering (DLS). The ameliorative effects of BMEs were evaluated using spectrophotometric assays for cellular viability/toxicity and oxidative stress. Results:Our results confirmed that Pb is a potent cytotoxic chemical, the exposure of which was associated with significant decreases in cellular viabilities in MTT reduction and lactate dehydrogenase (LDH) release assays. Additionally, Pb treatment increased the formation of reactive oxygen (ROS) and nitrogen (RNS) species. However, cotreatment with BMEs significantly mitigated Pb-induced oxidative stress and cellular damage. Conclusion:This study highlights the endogenous potential of BMEs as therapeutic and biotechnological agents against chemical toxicity.
Subhrajita Panda, Faraz AhmadDepartment of Integrative Biology, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, TN, 632014, IndiaCorrespondence: Faraz Ahmad, Department of Integrative Biology, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, TN, 632014, India, Email faraz.ahmad@vit.ac.inPurpose: Exosomes derived from mammalian milk are extracellular vesicular dietary agents capable of interspecies communication. Bovine milk exosomes (BMEs) are abundant natural nanovesicular resources that are enriched in bioactive components, including proteins, lipids, and microRNAs, and as such possess tremendous potential to affect cellular functions in the consumers. Although the applications of BMEs as delivery platforms for exogenous therapeutics are well known, their endogenous therapeutic potential remains relatively undiscerned. This study aimed to examine the cytoprotective role of BMEs as stand-alone therapeutic agents on human embryonic kidney (HEK293T) cells exposed to a prevalent environmental toxicant, lead (Pb).Methods: Isolation of BMEs was performed using standardized ultracentrifugation-based protocols. The physico-biochemical characterization of BMEs was performed using electron microscopy, Western blotting and dynamic light scattering (DLS). The ameliorative effects of BMEs were evaluated using spectrophotometric assays for cellular viability/toxicity and oxidative stress.Results: Our results confirmed that Pb is a potent cytotoxic chemical, the exposure of which was associated with significant decreases in cellular viabilities in MTT reduction and lactate dehydrogenase (LDH) release assays. Additionally, Pb treatment increased the formation of reactive oxygen (ROS) and nitrogen (RNS) species. However, cotreatment with BMEs significantly mitigated Pb-induced oxidative stress and cellular damage.Conclusion: This study highlights the endogenous potential of BMEs as therapeutic and biotechnological agents against chemical toxicity.Keywords: exosomes, HEK293T cell line, isolation method, oxidative stress, viability, redox signaling
Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of immune dysregulation. Here, we presented the case of a young male diagnosed with psoriasis and Crohn's disease (CD), after multiple therapy failures, he started upadacitinib (UPA) in 2023. After induction and maintenance therapy, colonoscopy revealed suboptimal disease control. In November 2024, he was admitted to our hospital with fever and elevated liver enzymes, the final diagnosis was HSV-1-associated secondary HLH. After antiviral and hormonal treatment, the patient was discharged in stable condition. This case illustrates that HLH in such patients is rarely attributable to a single drug, rather, it results from the convergence of underlying CD, cumulative multi-agent immunosuppression, and an acute infectious trigger (HSV-1). Clinicians should maintain high vigilance for virus-associated HLH in heavily immunosuppressed IBD patients.
Rationale:Interleukin-33 (IL-33) is a key orchestrator of broad-spectrum downstream host-response mechanisms, including inflammation, tissue homeostasis, and repair. Dysregulation of IL-33 signaling is associated with several pathological conditions. The FRONTIER program comprised four phase 2 signal-finding studies of tozorakimab, an anti-IL-33 human immunoglobulin G1 monoclonal antibody, in diabetic kidney disease (FRONTIER-1), moderate-to-severe atopic dermatitis (FRONTIER-2), moderate-to-severe asthma (FRONTIER-3), and moderate-to-severe chronic obstructive pulmonary disease and chronic bronchitis (FRONTIER-4). This analysis assessed the safety data from these clinical studies. Methods:FRONTIER-1-4 were randomized, double-blind, placebo-controlled studies evaluating the efficacy, safety, pharmacokinetics, and immunogenicity of tozorakimab in adults. Participants received subcutaneous tozorakimab (FRONTIER-1, 30-300 mg; FRONTIER-2, 60-600 mg; FRONTIER-3, 300-600 mg; FRONTIER-4, 600 mg) or placebo every 4 weeks for 4-7 doses, with follow-up periods ranging from 24-36 weeks from the first dose. Safety (adverse events [AEs], serious AEs, and AEs of special interest) and immunogenicity endpoints from the FRONTIER studies were summarized. Results:In total, 1076 patients were included in this analysis (tozorakimab, n=738; placebo, n=338). Deaths occurred only in FRONTIER-1, in similar proportions between treatment groups (tozorakimab, 0.9%; placebo, 0.8%), and were unrelated to tozorakimab. The proportion of participants experiencing at least one treatment-emergent AE (TEAE) or serious TEAEs was generally similar between tozorakimab and placebo groups. The proportion of participants experiencing AEs of special interest, including events of progression of heart failure, was low (tozorakimab, 0.0-1.5%; placebo, 0.0-0.8%), with no meaningful differences between groups; the frequency of injection-site reactions was however higher in tozorakimab than in placebo recipients (tozorakimab, 1.2-20.9%; placebo, 0.0-4.9%). No clinically significant trends were observed in laboratory or vital-sign parameters, and immunogenicity was low. Conclusion:Tozorakimab was well tolerated across a range of inflammatory diseases, with no safety concerns identified.
The interleukin-17A (IL-17A) cytokine is a key driver in the pathogenesis of chronic immune-mediated diseases, including psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). As a central proinflammatory mediator, IL-17A signals through the IL-17RA/RC receptor complex to promote tissue-specific inflammation. This narrative review outlines the therapeutic rationale for targeting IL-17A and summarizes the current evidence for vunakizumab, a novel humanized monoclonal antibody against IL-17A. We reviewed the biological basis of IL-17A signaling and its pathogenic role in PsO, PsA, and AS. We then synthesized the pharmacokinetic properties of vunakizumab and the clinical evidence from Phase II and III trials evaluating its efficacy and safety. Post hoc analyses across a broad range of clinically relevant patient subgroups further support the consistency of its therapeutic effects. Clinical trial data demonstrate that vunakizumab offers robust efficacy and a favorable safety profile in the treatment of psoriasis and spondyloarthritis (including PsA and AS). Its properties are comparable to other approved IL-17A inhibitors, establishing it as a promising therapeutic option for these IL-17A-mediated diseases.
Hongzhuo Yan,1,2,* Yu Chen,3,* Yali Song,1 Min Yan,1 Kexiang Yan1 1Dermatology Diagnosis and Treatment Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China; 3The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kexiang Yan, Email ykx2292002@aliyun.comAbstract: The interleukin-17A (IL-17A) cytokine is a key driver in the pathogenesis of chronic immune-mediated diseases, including psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). As a central proinflammatory mediator, IL-17A signals through the IL-17RA/RC receptor complex to promote tissue-specific inflammation. This narrative review outlines the therapeutic rationale for targeting IL-17A and summarizes the current evidence for vunakizumab, a novel humanized monoclonal antibody against IL-17A. We reviewed the biological basis of IL-17A signaling and its pathogenic role in PsO, PsA, and AS. We then synthesized the pharmacokinetic properties of vunakizumab and the clinical evidence from Phase II and III trials evaluating its efficacy and safety. Post hoc analyses across a broad range of clinically relevant patient subgroups further support the consistency of its therapeutic effects. Clinical trial data demonstrate that vunakizumab offers robust efficacy and a favorable safety profile in the treatment of psoriasis and spondyloarthritis (including PsA and AS). Its properties are comparable to other approved IL-17A inhibitors, establishing it as a promising therapeutic option for these IL-17A–mediated diseases.Keywords: IL-17A, psoriasis, psoriatic arthritis, ankylosing spondylitis, vunakizumab
Introduction:Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disorder driven by pulmonary vascular remodeling, with high morbidity and mortality. Current therapies only alleviate symptoms and cannot reverse disease progression. Our previous study has demonstrated that microRNA-661 (miR-661) inhibits Human pulmonary artery smooth muscle cell (HPASMC) and Human pulmonary artery endothelial cell (HPAEC) proliferation, but its underlying molecular mechanism in PAH remains unclear. This study aimed to identify the target gene of miR-661 and elucidate its regulatory role in PAH pathogenesis, seeking novel therapeutic targets for this incurable disease. Methods:Serum samples from 12 PAH patients and 12 healthy volunteers were enrolled this research. Human pulmonary artery smooth muscle cells (HPASMCs) and endothelial cells (HPAECs) were cultured under normoxic or hypoxic conditions. MiR-661 mimics/inhibitors and CCND2 plasmids were transfected into cells. RNA-seq screened differentially expressed genes, and dual-luciferase reporter assay verified the target binding of miR-661. RT-qPCR and Western blot detected gene/protein expression, while MTT, EdU, Transwell and flow cytometry assessed cell proliferation, migration and cycle progression. Results:We perform RNA-seq and luciferase assay and found that CCND2 is a direct miR-661 target that is repressed via 3'UTR binding. miR-661 is lower expressed while the expression of CCND2 is higher in PAH patient serum and hypoxic HPASMCs/HPAECs, showing a significant negative correlation. CCND2 overexpression promoted pulmonary artery cell cycle progression, proliferation and migration under hypoxia, while miR-661 overexpression reversed these effects. In addition, we found that Stattic, a specific inhibitor of STAT3 (an upstream regulatory protein of CCND2), could inhibit HPASMC cell proliferation and migration and this effect is enhanced by miR-661. Discussion:This study clarifies that miR-661 suppresses HPASMC and HPAEC proliferation or migration by targeting CCND2, and the miR-661/CCND2 axis is a key regulatory pathway in PAH-related vascular remodeling. Hypoxia-induced miR-661 downregulation leads to CCND2 accumulation, driving abnormal pulmonary artery cell biological behaviors. miR-661/CCND2 axis regulates PAH progression, providing a potential therapeutic target.
Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, even with many therapeutic interventions, including surgery, chemotherapy, and radiotherapy. Recent immunotherapies have broaden horizons to the utilization of the immune system to eradicate GBM. However, the clinical efficacy of such approaches is limited, owing to the tumor's multifaceted immunosuppressive microenvironment and the blood-brain barrier (BBB) structure. The dysfunction of immune cells, especially T cells and natural killer (NK) cells, is significantly influenced by the immunosuppressive mechanisms in GBM. Novel therapeutic strategies are needed to overcome these mechanisms. In the current review, we explore the main functions of T cells, especially cytotoxic CD4+ and helper CD8+ T cells, alongside NK cells, in response to GBM. We further discuss the mechanisms contributing to their dysfunction, focusing on T cell exhaustion, altered receptor expression, and metabolic reprogramming within the GBM microenvironment to establish diagnostic and prognostic biomarkers. Moreover, we highlight recent advances in immunotherapeutic approaches, including immune checkpoint inhibitors (ICI), miRNA therapy, oncolytic viruses, and Chimeric Antigen Receptor (CAR) T/NK cell therapy to provide new opportunities for enhancing GBM treatment and biomarker-guided precision medicine.
Psoriasis is a chronic, immune-mediated inflammatory disease. Despite significant advancements in therapies, a considerable subset of patients either fails to achieve adequate response or experiences adverse effects. Herein, we present the case of a patient with a 20-year history of psoriasis, refractory to topical therapy. She received low-dose interleukin-2 (IL-2) monotherapy (500,000 IU subcutaneously daily for 80 consecutive days). A prompt and marked clinical improvement was noted. No adverse events were reported, and the patient remained free of new lesions after treatment discontinuation. To our knowledge, this is the first case of psoriasis successfully treated with low-dose IL-2 monotherapy, suggesting that this approach may represent a rapid and effective alternative for patients with psoriasis. Further evaluation in larger clinical studies is warranted.
Generalized pustular psoriasis (GPP) is a severe and potentially life-threatening form of psoriasis. Although spesolimab, an inhibitor of the interleukin (IL)-36 pathway, has been approved for the treatment of GPP, access to this agent remains limited. Vunakizumab, a humanized IgG1/κ monoclonal antibody that selectively neutralizes interleukin (IL)-17A inhibitors, is not yet approved for GPP. We herein report a 72-year-old male with a 40-year history of plaque psoriasis who developed GPP refractory to methotrexate combined with guselkumab and acitretin (20 mg/day). Following switching to vunakizumab (240 mg intravenously every 2 weeks) in combination with acitretin (40 mg/day), the patient achieved a GPPASI 75 response within 2 weeks and near-complete clearance (GPPASI ≈ 100) by week 12. Six induction doses of vunakizumab were administered, and acitretin was tapered to 20 mg/day for long-term maintenance. Throughout 36 weeks of follow-up, no disease relapse or drug-related adverse events were observed. This case, together with a review of the literature, provides support for IL-17A blockade combined with acitretin as a feasible and fast-acting regimen for refractory GPP in elderly patients.
Background: Venous malformations (VMs) are slow-flow vascular anomalies frequently driven by somatic activating mutations in TEK/TIE2 receptor. Medical treatment options remain limited; while mTOR inhibition with sirolimus has shown moderate benefit, direct TIE2 inhibition has a strong biological rationale and emerging clinical evidence. Case Presentation: We report a 51-year-old patient with a diffuse VM involving the right cervical region, thorax, and upper extremity, associated with a somatic mosaic TEK (L914F) variant. The disease was refractory to conventional therapies and complicated by chronic coagulopathy. Compassionate-use treatment with the selective TIE2 inhibitor rebastinib was initiated based on a previously reported patient. Over 3 years of follow-up, the patient experienced sustained clinical benefit with decreased pain and inflammation, partial volume reduction, functional improvement, and stabilization of coagulopathy with manageable toxicity. Unfortunately, the interruption in the production of the drug made it necessary to try other less specific alternatives like PI3K inhibitor alpelisib. Conclusion: This second long-term clinical experience supports the sustained efficacy and safety of TIE2 inhibition in selected TEK-mutated VMs and highlights the therapeutic gap arised from drug discontinuation, underscoring the need for alternative targeted strategies and prospective evaluation.
Background:Recombinant human interferon gamma (rhIFN-γ) and monoclonal antibodies are promising biomolecules for improving clinical medicines worldwide due to their biomedical applications. However, most African countries lack established production protocols. Although Freund's Complete Adjuvant (FCA) has been widely used to enhance antibody production, it has been reported to cause adverse effects. This study aimed to optimize the expression and purification of rhIFNγ and develop an immunization protocol for producing optimal humoral responses using alternative adjuvants such as RIBI Immunochem (RIBI) adjuvant and Freund's Incomplete Adjuvant (FIA), with FCA as the standard. Methodology:The human interferon gamma (NM000619.3) sequence was retrieved from NCBI and sent to GenScript for codon optimization and construct synthesis. The constructs were transformed into E. coli BL-21, and protein expression was induced with IPTG. The expression and purification conditions were optimized. To evaluate immunization regimens and alternative adjuvants to FCA, three groups of female BALB/c mice were immunized with varying concentrations of rhIFNγ (25, 50, and 100 µg) mixed with an equal volume of RIBI adjuvant, FIA, and FCA. An Enzyme-Linked Immunosorbent Assay was used to measure antibody levels from each group. Results:The study identified 0.6 mM of IPTG at 37°C and 250 rpm for 4 hours as the optimal conditions for rhIFNγ expression. Increasing imidazole concentration in wash and elution buffers enhanced rhIFNγ purity but reduced protein yield. Administration of 100 µg of rhIFNγ with RIBI adjuvant elicited a sufficient immune response, while higher concentrations of FCA and FIA increased side effects, indicating the need for lower adjuvant doses. Conclusion:Although FCA has been reported to produce high antibody titers with notable side effects, this study found no significant difference in antibody levels between mice immunized with 100 µg rhIFNγ mixed with FCA and the group immunized with 100 µg rhIFNγ plus RIBI adjuvant.
Gastric ulcer disease remains a significant global health concern, with Helicobacter pylori (H. pylori) infection being a primary etiological factor. Conventional therapies are increasingly limited by antibiotic resistance, treatment failure, and adverse effects. In this context, phytomedicine has emerged as a promising complementary and alternative therapeutic approach. This review systematically discusses the key mechanisms by which phytomedicines enhance gastric mucosal defense, including antioxidant activity, anti-inflammatory modulation, inhibition of urease and bacterial adhesion, suppression of virulence factors, and restoration of epithelial barrier integrity. Plant-derived bioactive compounds demonstrate multi-targeted gastroprotective effects through modulation of oxidative stress, cytokine signaling, prostaglandin synthesis, and tight junction preservation. While preclinical and limited clinical evidence support their therapeutic potential, further well-designed clinical trials and standardized phytochemical formulations are required to validate translational applicability.
Rheumatoid factor (RF), which is an autoantibody that is predominantly targeted at the Fc region in IgG, has been a key point of diagnosis and prognostication of rheumatoid arthritis (RA). There is, however, an emergent body of evidence that RF positivity, including in persons with preexisting autoimmune disease as well as asymptomatic seropositive persons, can indicate more global immune dysregulation with consequences of cardiometabolic and hepatic health. RF is involved in the development of circulating immune complexes, which increases inflammation through complement activation, Fc receptor interaction and cytokine release. These routes are becoming well-known mechanistic causes of cardiometabolic diseases, such as atherosclerosis, insulin resistance, metabolic syndrome, and heart failure. Similarly, the immune-complex deposition and chronic inflammatory signaling also play a role in hepatic injury, metabolic dysfunction-associated fatty liver disease (MAFLD) and fibrosis. The present review summarizes the existing information about the role of RF as a predictor and a possible mediator of cardiometabolic and hepatic dysfunction in chronic diseases. We searched scientific databases for epidemiologic relationships, possible biological pathways, and clinical implications for risk stratification and integrated care. RF could serve as an accessible biomarker of systemic inflammatory risk, complementing its traditional role in rheumatology and, within the framework of precision medicine, helping to guide early detection and preventive strategies across diverse clinical populations.
Objective:To systematically evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for patients with Multiple System Atrophy (MSA) by synthesising available clinical trial evidence and clarifying signals of disease modification. Background:MSA is a rapidly progressive and fatal neurodegenerative disorder for which no disease-modifying therapies exist. MSC therapy has emerged as a potential treatment, with mechanisms centered on neuroprotection and clinical benefit through anti-inflammatory and trophic effects rather than direct cell replacement. Methods:We systematically searched PubMed, Scopus, the Cochrane Library, and Web of Science for studies on mesenchymal stem cell (MSC) therapy in adults with probable or confirmed multiple system atrophy (MSA). Eligible studies included single-arm trials or comparisons with placebo or usual care. The primary outcome was safety and tolerability, assessed by the type and severity of adverse events. Secondary outcomes included the rate of disease progression measured by UMSARS total, Part I, and Part II scores. Results:A total of 123 participants from seven studies were included. MSCs were administered through multiple routes, and adverse events occurred in 65-70% of participants but were mostly mild and transient. No serious MSC-related toxicity was reported. Several studies suggested slower disease progression following MSC therapy. For example, in Singer et al (2019), patients receiving high-dose MSCs showed a markedly lower rate of UMSARS total score progression compared with a matched historical control group (0.40 ± 0.59 vs 1.44 ± 1.42 points/month, p = 0.004), suggesting a possible dose-dependent effect. However, treatment effects varied across studies depending on dose, administration route, and disease stage. Conclusion:MSC therapy shows potential for disease modification in MSA by slowing neurological deterioration. The treatment was well tolerated, supporting the need for larger, definitive trials with standardised protocols and longer follow-up to confirm clinical benefit.
Noon Elimam,1 Shams Samih Albarari,2 Yara Shaalan,3 Shazaa Mahmoud Elsheikh,4 Ainaa A Alzamari,5 Nourhan Elmekkawi,6 Rahaf Mogahed,7 Razan H Alghuweiri8 1Department of Neurology, Faculty of Medicine, Bogomolets National Medical University, Kyiv, Ukraine; 2Department of Neurology, Faculty of Medicine, Tbilisi State Medical University, Tbilisi, Georgia; 3Department of Neurology, Faculty of Medicine, Misr University for Science and Technology, 6th of October City, Egypt; 4Department of Clinical Pharmacology, Benha Faculty of Medicine, Benha, Egypt; 5Department of Pediatrics, Palestinian Medical Complex, Al-Quds University, Ramallah, Palestine; 6Department of Clinical Pharmacy, Zifta General Hospital, Zifta, Egypt; 7Department of Neurology, Faculty of Medicine, 6th of October University, 6th of October City, Egypt; 8Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanCorrespondence: Noon Elimam, Email Noonsiddig@gmail.comObjective: To systematically evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for patients with Multiple System Atrophy (MSA) by synthesising available clinical trial evidence and clarifying signals of disease modification.Background: MSA is a rapidly progressive and fatal neurodegenerative disorder for which no disease-modifying therapies exist. MSC therapy has emerged as a potential treatment, with mechanisms centered on neuroprotection and clinical benefit through anti-inflammatory and trophic effects rather than direct cell replacement.Methods: We systematically searched PubMed, Scopus, the Cochrane Library, and Web of Science for studies on mesenchymal stem cell (MSC) therapy in adults with probable or confirmed multiple system atrophy (MSA). Eligible studies included single-arm trials or comparisons with placebo or usual care. The primary outcome was safety and tolerability, assessed by the type and severity of adverse events. Secondary outcomes included the rate of disease progression measured by UMSARS total, Part I, and Part II scores.Results: A total of 123 participants from seven studies were included. MSCs were administered through multiple routes, and adverse events occurred in 65– 70% of participants but were mostly mild and transient. No serious MSC-related toxicity was reported. Several studies suggested slower disease progression following MSC therapy. For example, in Singer et al (2019), patients receiving high-dose MSCs showed a markedly lower rate of UMSARS total score progression compared with a matched historical control group (0.40 ± 0.59 vs 1.44 ± 1.42 points/month, p = 0.004), suggesting a possible dose-dependent effect. However, treatment effects varied across studies depending on dose, administration route, and disease stage.Conclusion: MSC therapy shows potential for disease modification in MSA by slowing neurological deterioration. The treatment was well tolerated, supporting the need for larger, definitive trials with standardised protocols and longer follow-up to confirm clinical benefit.Plain Language Summary: Multiple System Atrophy (MSA) is a rare, rapidly worsening brain disorder that affects movement, balance, and automatic body functions, and there are currently no treatments that can slow its progression. Mesenchymal stem cell (MSC) therapy has been suggested as a possible treatment because it may protect nerve cells and reduce inflammation rather than replace damaged neurons. We reviewed all clinical trials testing MSC therapy in adults with MSA to evaluate safety and possible effectiveness. Major medical databases were searched, and studies reporting side effects and changes in disease severity over time using a standard clinical rating scale were included. Seven studies with 123 patients were included. MSCs were given through different routes, including blood vessels, spinal fluid, or near the brain. Most patients experienced mild, short-term side effects, such as fever or headache, and no serious treatment-related problems were reported. Across studies, patients receiving MSC therapy showed slower worsening of symptoms than expected, particularly in earlier stages of MSA. While these findings are encouraging, the included studies were small and varied in design, which limits the strength of the conclusions. Larger, well-designed clinical trials are needed to determine whether MSC therapy can provide sustained clinical benefits for patients with MSA.Keywords: cerebellar dysfunction, immunomodulation, mesenchymal stem cells, multiple system atrophy, neurodegeneration, neuroprotection, Parkinsonism
Chronic migraine (CM) is a disabling neurological disorder for which calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies, such as erenumab, provide effective prophylaxis. Although generally well tolerated, rare neuromuscular complications resembling ocular myasthenia gravis (MG) have been reported. A 46-year-old woman with CM achieved marked improvement with erenumab for over three years before developing diplopia and intermittent ptosis. Laboratory and imaging studies were unremarkable, but clinical suspicion for MG led to pyridostigmine therapy, resulting in rapid improvement. Brief episodes of dysarthria occurred but resolved within one month. Symptoms disappeared after discontinuation of erenumab and continued pyridostigmine. On re-initiation of erenumab, the patient maintained migraine control without recurrence of MG-like symptoms. This case illustrates a rare, late-onset, reversible MG-like complication of erenumab. Clinicians should remain alert to ocular manifestations even as delayed adverse effects of anti-CGRP therapy.
Oral manifestations are a frequent yet underrecognized feature of systemic lupus erythematosus (SLE), contributing substantially to patient morbidity and reduced quality of life. They are insufficiently represented in clinical outcome measures and therapeutic guidelines, despite their clinical relevance. We report the case of a 39-year-old woman with SLE who developed severe, refractory tongue ulcers and glossodynia persisting for three years, unresponsive to hydroxychloroquine (HCQ), azathioprine (AZA), colchicine, methotrexate (MTX), and glucocorticoids (GC). Belimumab was discontinued due to gastrointestinal intolerance and lack of efficacy on oral lesions. The patient was subsequently treated with anifrolumab 300 mg intravenously every four weeks. After the first infusion, oral ulcers resolved, arthritis improved, and corticosteroids were discontinued. Within three months, the tongue lesions had completely healed, enabling unrestricted oral intake and full resumption of professional activities. Clinical remission was maintained on anifrolumab and hydroxychloroquine alone at four months of follow-up. This case highlights the therapeutic challenge of refractory oral lesions in SLE, a manifestation not adequately addressed in current EULAR (2023 update) or ACR (2025) guidelines. While conventional immunosuppressants such as azathioprine, methotrexate, and mycophenolate mofetil remain options, their efficacy for isolated oral lesions is limited. Emerging evidence, including case reports and small series, suggests that anifrolumab may provide significant benefit for mucosal involvement. The key learning point is that refractory tongue involvement may represent a dominant and treatment-resistant manifestation of SLE, yet it can respond to targeted biologic therapy such as anifrolumab and our report adds to this growing body of evidence. Prospective comparative studies and registry analyses are required to define anifrolumab's effectiveness specifically for refractory oral manifestations and to compare outcomes with other biologics.
Olena Garmish,1,* Svitlana Smiyan,2,* Roman Komorovsky,2 Ivan Bilozetskyi3 1King’s College Hospital London, Dubai, United Arab Emirates; 2Department of Internal Medicine II, Ivan Horbachevsky Ternopil National Medical University, Ternopil, Ukraine; 3Clinic of Facial Aesthetics and Surgery, Ternopil, Ukraine*These authors contributed equally to this workCorrespondence: Roman Komorovsky, Email komorovsky@tdmu.edu.uaAbstract: Oral manifestations are a frequent yet underrecognized feature of systemic lupus erythematosus (SLE), contributing substantially to patient morbidity and reduced quality of life. They are insufficiently represented in clinical outcome measures and therapeutic guidelines, despite their clinical relevance. We report the case of a 39-year-old woman with SLE who developed severe, refractory tongue ulcers and glossodynia persisting for three years, unresponsive to hydroxychloroquine (HCQ), azathioprine (AZA), colchicine, methotrexate (MTX), and glucocorticoids (GC). Belimumab was discontinued due to gastrointestinal intolerance and lack of efficacy on oral lesions. The patient was subsequently treated with anifrolumab 300 mg intravenously every four weeks. After the first infusion, oral ulcers resolved, arthritis improved, and corticosteroids were discontinued. Within three months, the tongue lesions had completely healed, enabling unrestricted oral intake and full resumption of professional activities. Clinical remission was maintained on anifrolumab and hydroxychloroquine alone at four months of follow-up. This case highlights the therapeutic challenge of refractory oral lesions in SLE, a manifestation not adequately addressed in current EULAR (2023 update) or ACR (2025) guidelines. While conventional immunosuppressants such as azathioprine, methotrexate, and mycophenolate mofetil remain options, their efficacy for isolated oral lesions is limited. Emerging evidence, including case reports and small series, suggests that anifrolumab may provide significant benefit for mucosal involvement. The key learning point is that refractory tongue involvement may represent a dominant and treatment-resistant manifestation of SLE, yet it can respond to targeted biologic therapy such as anifrolumab and our report adds to this growing body of evidence. Prospective comparative studies and registry analyses are required to define anifrolumab’s effectiveness specifically for refractory oral manifestations and to compare outcomes with other biologics.Keywords: systemic lupus erythematosus, oral lesions, biological therapy, anifrolumab, treatment outcome
