Search Results (105)

Background/Objectives: Fibroblast-like synoviocytes (FLS) are key contributors to rheumatoid arthritis (RA) pathogenesis, driving synovial inflammation, cartilage degradation, bone erosion and disease persistence. Recent advances have revealed substantial FLS heterogeneity, with distinct fibroblast subsets exhibiting different pathogenic roles within the rheumatoid synovium. Although disease-modifying antirheumatic drugs (DMARDs) constitute the cornerstone of RA treatment, their effects on FLS have not been comprehensively characterised. This review summarises and compares the effects of conventional synthetic DMARDs (csDMARDs), biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) on RA-FLS. Methods: A non-systematic literature review was conducted to identify studies investigating the effects of DMARDs on RA-FLS. Studies evaluating the impact of csDMARDs, bDMARDs and tsDMARDs on FLS proliferation, apoptosis, migration, invasion, inflammatory mediator production, extracellular matrix remodelling and osteoclastogenic activity were included. Results: Available evidence indicates that DMARDs modulate multiple pathogenic functions of RA-FLS. Methotrexate, leflunomide, hydroxychloroquine and sulfasalazine regulate inflammatory signalling, apoptosis, autophagy and ferroptosis. Biologic agents, particularly tumour necrosis factor alpha (TNF-α) and interleukin (IL)-6 receptor inhibitors, suppress cytokine production, matrix metalloproteinase expression, osteoclastogenic signalling and FLS migration. Targeted synthetic DMARDs, particularly Janus kinase inhibitors (JAKis), exhibit broad activity across inflammatory, angiogenic, metabolic and tissue-destructive pathways. Despite their distinct molecular targets, all DMARD classes ultimately attenuate key pathogenic FLS functions associated with synovial inflammation and joint destruction. Conclusions: JAKis exert broad effects on RA-FLS function in vitro, likely reflecting their ability to block multiple cytokine-dependent signalling pathways. However, clinical evidence linking these effects to patient outcomes remains limited; further validation is therefore required. Full article

Anthracycline cardiotoxicity involves early oxidative–inflammatory injury to the myocardium and vasculature. Repurposing anti-inflammatory agents may offer pragmatic cardioprotection. The purpose of this study is to evaluate whether sulfasalazine (SSZ) mitigates doxorubicin (DOX)-induced myocardial and aortic injury in rats. Twenty-eight male Wistar albino rats were randomized to: Control (vehicle, n = 8), DOX (20 mg/kg i.p., single dose; n = 10), and SSZ + DOX (SSZ 300 mg/kg i.p. once daily for 3 days, then DOX 20 mg/kg i.p.; n = 10). At 24 h post-DOX, ECG and invasive blood pressure (BP) were recorded. The heart and thoracic aorta were harvested for histopathology and oxidative stress assays (MDA, SOD, GSH, CAT; composite indices where applicable). Compared with SSZ + DOX, the DOX group exhibited higher BP and greater arrhythmic burden. In the aorta, DOX elevated MDA and reduced SOD, GSH, and CAT versus the control, whereas SSZ + DOX shifted these toward control values. In the myocardium, DOX decreased SOD and increased oxidative index; SSZ + DOX attenuated histological injury (edema, hemorrhage, cardiomyocyte degeneration) and restored aortic intima–media thickness toward control. Heart rate was lower in SSZ + DOX than other groups. Short-course SSZ pretreatment alleviated early DOX-induced oxidative stress and structural damage in myocardial and aortic tissues, with concurrent improvement in hemodynamic and ECG profiles. These data support further dose–timing optimization and longer-term functional studies to define SSZ’s translational potential as an adjunct cardioprotective strategy during anthracycline exposure. Full article

The rapid emergence of carbapenem-resistant Acinetobacter baumannii has become a major health concern, primarily driven by the dissemination of class D β-lactamases, particularly OXA-23, which compromise the efficacy of last-line β-lactam antibiotics. Drug repurposing combined with structure-based computational approaches provides a promising strategy for accelerating the discovery of novel therapeutic candidates against multidrug-resistant pathogens. This study aimed to identify FDA-approved non-steroidal anti-inflammatory drugs (NSAIDS) with potential inhibitory activity against OXA-23 β-lactamase by using a comprehensive computational drug discovery workflow. Twenty-six FDA-approved NSAIDs were evaluated using an integrated computational pipeline comprising network pharmacology, KEGG pathway analysis, molecular docking, molecular dynamics simulations and ADMET profiling. KEGG pathway analysis confirmed the central role of OXA-23 in β-lactam resistance, while network pharmacology prioritized nine candidates NSAIDS for subsequent structure-based investigation. Molecular docking was performed using the crystal structure of OXA-23 β-lactamase (PDB ID: 4K0X), followed by molecular dynamics simulations to assess the stability of the protein–ligand complexes. Among the prioritized compounds, sulfasalazine demonstrated the most favorable predicted binding affinity (−8.3 kcal/mol), forming stable interactions with key catalytic residues, including SER126, VAL128, and LEU166 and exhibiting a more favorable docking profile than the reference drug imipenem (−5.7 kcal/mol). Molecular dynamics simulations supported the structural stability of the sulfasalazine OXA-23 complex throughout the simulation period. Furthermore, ADMET analysis indicated favorable pharmacokinetic characteristics including good oral bioavailability, high gastrointestinal absorption, low central nervous system penetration, and an acceptable predicted safety profile. This integrated computational study identifies sulfasalazine as a promising repurposing candidate for targeting OXA-23 β-lactamase in carbapenem-resistant A. baumannii. The findings demonstrate the utility of combining network pharmacology with molecular modeling to prioritize candidate therapeutics and provide a computational framework for accelerating antimicrobial drug discovery. Experimental validation is warranted to confirm the inhibitory activity and therapeutic potential of sulfasalazine against multidrug-resistant A. baumannii. Full article

Colorectal cancer (CRC) is a major cause of cancer-related mortality among adults younger than 50 years of age, and many tumors show incomplete response or develop resistance to 5-fluorouracil (5-FU)-based chemotherapy. Therefore, new therapeutic approaches that improve CRC sensitivity to existing chemotherapeutic agents are needed. KRAS-associated signaling contributes to CRC growth, metabolic adaptation and treatment resistance. In this study, we investigated whether sulfasalazine (SSZ), a U.S. Food and Drug Administration (FDA)-approved anti-inflammatory drug, could enhance the response of CRC cells to 5-FU and modulate KRAS/mitogen-activated protein kinase (MAPK)-associated signaling. Public dataset analysis using cBioPortal, Kaplan–Meier Plotter and DepMap showed that KRAS is commonly altered in CRC. The analysis also showed that higher KRAS expression was associated with shorter overall survival in 1061 CRC patients, while CRC cell-line models demonstrated KRAS dependency. In 2D cultures, both KRAS-mutant HCT116 and KRAS-wild-type RKO cells showed lower cell viability, reduced colony formation and decreased KRAS expression after SSZ treatment. In 3D cultures, exposure to SSZ reduced early spheroid formation, both as a single treatment and when combined with 5-FU. In established spheroids, SSZ-containing treatments affected cell viability, spheroid growth and morphology, with the most noticeable suppressive effect observed in RKO aggregates. SynergyFinder+ dose-matrix analysis identified dose ranges where SSZ and 5-FU showed additive-to-synergistic effects, leading us to select 600 μM SSZ with 25 μM 5-FU for further validation. Western blot results from PEGDA microwell-derived 3D spheroids showed that SSZ + 5-FU treatment reduced KRAS expression and affected KRAS/MAPK-related signaling. This effect was more pronounced in RKO cells, where downstream pathway suppression was stronger. The combination treatment also increased apoptosis-associated PARP cleavage. At the same time, it reduced Cyclin D1 and GPX4 protein levels and changed the expression of stemness-related markers, including ALDH1A3, CD44, and CD133. Together, these results support SSZ as a candidate repurposed adjuvant that may improve the response to 5-FU in CRC spheroid models and support the use of PEGDA microwell-based 3D platforms for testing combination therapy approaches. Full article

Lymphoplasmacytic gastritis (LPG) is one of the most prevalent chronic diseases affecting cheetahs (Acinonyx jubatus) under human care, yet its underlying cause remains unresolved. Gastric inflammation occurs in the majority of adult captive cheetahs but is uncommon in free-ranging populations, suggesting that management-related factors contribute to disease pathogenesis. This review proposes that LPG represents a bile acid-driven gastroenteropathy arising from disruption of the natural feeding ecology of the cheetah. In free-ranging systems, cheetahs consume large episodic meals separated by prolonged fasting intervals and ingest whole-prey containing substantial connective tissue and collagen. In captivity, feeding patterns are typically characterized by smaller, more frequent meals and diets dominated by lean skeletal muscle with reduced structural complexity. I hypothesize that this mismatch alters gastric emptying kinetics, disrupts coordinated pancreatic and biliary secretion, and destabilizes fat digestion. Inefficient lipolysis may impair micelle formation and promote bile acid mislocalization within the gastrointestinal tract, increasing mucosal exposure to hydrophobic bile acids capable of inducing chemical epithelial injury. Within this framework, lymphoplasmacytic gastritis is interpreted as a secondary inflammatory reaction to chronic bile acid-mediated mucosal stress rather than a primary immune-mediated disorder. The model also provides a mechanistic explanation for the frequent coexistence of gastritis with fat and protein maldigestion in captive cheetahs. Differential responses to antimicrobial therapy, glucocorticoids, sulfasalazine, pancreatic enzyme supplementation, and bile acid-modifying agents are broadly consistent with this proposed mechanism. Recognition of LPG as a physiologically driven gastroenteropathy has important implications for management, emphasizing restoration of feast–fast feeding patterns, inclusion of collagen-rich carcass components, and targeted modulation of bile acid composition and signaling. Full article

Background and clinical significance: Autoimmune hepatitis (AIH) and ankylosing spondylitis (AS) are distinct immune-mediated disorders that only rarely coexist. Diagnostic interpretation becomes especially challenging when the liver biochemistry is not classically hepatocellular and the histology is unavailable. Case presentation: We report a 51-year-old man with inflammatory back pain, polyarthralgia, weight loss, fatigue, night sweats and fever. Laboratory tests showed marked systemic inflammation, anemia and a cholestatic-predominant liver profile with associated aminotransferase elevation. Imaging demonstrated bilateral sacroiliitis and syndesmophytosis. Liver workup excluded viral, obstructive, metabolic, hereditary and inflammatory bowel disease-associated cholangiopathic causes. Antinuclear antiboidies (ANA) and anti liver cyotsole 1 antiboidies (anti-LC-1) were positive, IgG was mildly elevated, magnetic resonance cholangio-pancreatography (MRCP) was negative for primary sclerosing cholangitis and the simplified AIH score was six. A liver biopsy was proposed but refused. The patient received a short course of prednisone for rheumatologic flare control, followed by nonsteroidal anti-inflammatory treatment and sulfasalazine, with normalization of liver tests during follow-up. Conclusions: This case is suggestive, but not diagnostic, of autoimmune hepatitis in a patient with ankylosing spondylitis. In the absence of histology and in the setting of a cholestatic-predominant biochemical profile, the findings may be more appropriately interpreted as an autoimmune hepatitis-like syndrome. The main teaching point is that abnormal liver tests in AS warrant structured evaluation beyond drug toxicity and viral hepatitis, particularly when autoimmune serology is positive, even in a cholestatic-predominant presentation. Full article

Background: Inflammatory bowel disease (IBD) is frequently complicated by secondary bone loss driven by chronic inflammation and gut–bone axis dysregulation. Although dried ginger has pharmacological activities relevant to intestinal inflammation, the effects of dried ginger milk extract (DGME), a lipophilic constituent-enriched preparation, on IBD-associated bone loss (IBD-BL) remain unknown. This study evaluated the preventive and therapeutic effects of DGME on IBD-BL and explored the underlying mechanisms. Methods: Mice with DSS-induced IBD-BL were treated with DGME (250, 125, or 62.5 mg/kg) or sulfasalazine. Colitis severity, bone microarchitecture, osteoclast activity and Th17 cells were assessed by histology, micro-computed tomography, histomorphometry and flow cytometric analysis. UHPLC-Q-TOF MS, network pharmacology, 16S rRNA sequencing, fecal metabolomics, and in vitro assays were used for mechanistic investigation. Results: DGME ameliorated colitis, improved trabecular bone microarchitecture, and reduced osteoclast-related bone destruction. These effects were associated with selective suppression of pathogenic bone marrow TNF-α⁺ Th17 cells and downregulation of Il17a, Rorc, Tnfα, Ccr2, Ccr6, Cxcr4, Csf1, and Tnfsf11. Compared with aqueous extract, DGME was enriched in 19 lipophilic constituents. Multi-omics analyses showed that DGME remodeled gut microbiota and metabolite profiles, characterized by enrichment of Lactobacillus, Anaerotruncus, vanillin, and spermidine. Both vanillin and spermidine suppressed Th17 effector genes and inhibited MEK/ERK signaling in vitro. Conclusions: DGME alleviated IBD-BL by suppressing pathogenic TNF-α⁺ Th17 responses and remodeling the gut microbiota–metabolite axis. This study not only extends the therapeutic application of dried ginger from intestinal inflammation to IBD-BL, but also identifies vanillin and spermidine as candidate functional mediators linked to MEK/ERK inhibition. Full article

Chagas disease affects millions of people worldwide, including those in Latin America. The only drugs available for its treatment are benznidazole and nifurtimox. However, these drugs present high toxicity and limited efficacy. Therefore, the search for new treatments continues. In this regard, computer-assisted drug design has been implemented in scientific research for drug repurposing, allowing for reduced costs and time. Therefore, the objective of this work was to search for analogs of FDA-approved drugs with activity against Trypanosoma cruzi through ligand-based virtual screening and their biological evaluation against blood trypomastigotes. The compound TD-095 (LC₅₀ = 48.60 and 13.75 µM), a ketanserin analogue, TS-936 (LC₅₀ = 71.55 and 37.54 µM), a terfenadine analogue, and TD-831 (LC₅₀ = 75.94 and 26.17 µM), a sulfasalazine analogue, were considered as potential trans-sialidase inhibitors; TIM-967 (LC₅₀ = 69.70 and 39.69 µM) and LK-284 (LC₅₀ = 116.7 and 82.29 µM), two sulfonylurea analogues, were considered as potential triosephosphate isomerase inhibitors, showing better trypanocidal activity against NINOA and INC-5 strains, respectively, than the reference drugs. Molecular dynamics simulations predicted the stability of the compounds in complex with their respective proteins. Finally, the ADMET predictive analysis showed favorable properties for the compounds. These results support continued research into new agents against Trypanosoma cruzi, using structures of drugs already approved by the FDA. Full article

Background/Objectives: Patients with rheumatic immune-mediated inflammatory diseases (R-IMID) require latent tuberculosis infection screening and, in case of positivity, chemoprophylaxis. Isoniazid INH remains the standard regimen, but hepatotoxicity is an underrecognized concern. To describe the characteristics of R-IMID patients developing hepatotoxicity during INH therapy and identify potential risk factors through clinical analysis and literature review. Methods: Retrospective study of 64 R-IMID who developed hepatotoxicity with INH. Mean age was 53.4 ± 10.5 years; 70.3% female. Diagnoses included spondyloarthritis/psoriatic arthritis (56.3%), rheumatoid arthritis (32.8%), systemic sclerosis (4.7%), connective tissue diseases (4.7%), and other IMIDs (3.2%). All patients showed ≥ 2 × upper limit of normality (ULN) liver enzyme elevation, 34.4% ≥ 3 ULN, 20.3% ≥ 4 ULN. Literature review (19 studies) revealed INH-related hepatotoxicity rates of 1–41%, exacerbated by concurrent methotrexate, sulfasalazine, TNF inhibitors, and prior drug-induced liver injury. Results: Hepatotoxicity was frequent when INH was combined with other hepatotoxic drugs, especially methotrexate. Conclusions: INH prophylaxis in R-IMID patients carries substantial hepatotoxic risk. Careful hepatic monitoring and individualized risk stratification are essential to prevent liver injury in immunosuppressed populations. Full article

Gliomas are the most common malignant primary brain tumors in adults. The treatment of high-grade gliomas is very limited due to their diffuse infiltration, high plasticity, and resistance to conventional therapies. Although they were long considered passive massive lesions, they are now regarded as functionally integrated components of neural circuits, as they form authentic electrochemical synapses with neurons. This allows them to mimic neuronal activity to drive tumor growth and invasion. Ultrastructural studies show presynaptic vesicles in neurons and postsynaptic densities in glioma cell membranes, while electrophysiological recordings detect postsynaptic currents in tumor cells. Tumor microtubules (TMs), dynamic cytoplasmic protrusions enriched in AMPA receptors, are the structures responsible for glioma–glioma and glioma–neuron connectivity, also contributing to treatment resistance and tumor network integration. In these connections, neurons release glutamate that mainly activates their AMPA receptors in glioma cells, while gliomas release excess glutamate, causing excitotoxicity, altering the local excitatory-inhibitory balance, and promoting a hyperexcitable and pro-tumorigenic microenvironment. In addition, certain gliomas, such as diffuse midline gliomas, have altered chloride homeostasis, which makes GABAergic signaling depolarizing and growth promoting. Synaptogenic factors, such as neuroligin-3 and BDNF, further enhance glioma proliferation and synapse formation. These synaptic and paracrine interactions contribute to cognitive impairment, epileptogenesis, and resistance to surgical and pharmacological interventions. High functional connectivity within gliomas correlates with shorter patient survival. Therapies such as AMPA receptor antagonists (perampanel), glutamate release modulators (riluzole or sulfasalazine), and chloride cotransporter inhibitors (NKCC1 blockers) aim to improve outcomes for patients. Full article

Proteoglycans and their fragments have potential as diagnostic or theragnostic biomarkers to identify diseases characterized by dysregulated extracellular matrix remodeling, such as juvenile idiopathic arthritis (JIA). Therefore, our study aimed to evaluate the diagnostic utility of plasma proteoglycan profiles, namely, aggrecan, decorin, and biglycan, released from osteoarticular structures into the blood of children with juvenile idiopathic arthritis. These profiles are potential biomarkers of tissue destruction and/or indicators of the efficacy of therapy with the biologic agent etanercept (ETA). This study was conducted on 263 blood samples collected from 25 healthy children and 34 children at various stages of juvenile idiopathic arthritis disease: immediately after diagnosis, following treatment with disease-modifying antirheumatic drugs (DMARD) (methotrexate, sulfasalazine, and prednisone), and during 3, 6, 12, 18, and 24 months of therapy with etanercept. Quantitative levels of aggrecan, biglycan, and decorin were measured using ELISA kits. In children with JIA, plasma aggrecan levels were elevated at diagnosis, decreased after ineffective DMARD therapy, and increased again at 24 months of etanercept treatment despite clinical improvement. By contrast, biglycan levels were similar to those in healthy controls but decreased during etanercept therapy. Decorin levels were initially high in untreated and DMARD-treated patients but returned to normal after 24 months of biologic treatment. After considering these findings and the ROC analysis, we conclude that decorin appears to be a promising biomarker for diagnosing and monitoring etanercept therapy in JIA, and biglycan is a useful biochemical marker for assessing the effectiveness of ETA treatment. Full article

This study presents a robust, data-driven framework for classifying and predicting drug solubility in deep eutectic solvents (DESs), moving beyond empirical approaches to enable rational formulation design. By analyzing 2010 solubility measurements of 21 diverse pharmaceutical compounds across numerous choline chloride, betaine, and menthol-based DESs, we employed Principal Component Analysis to reduce 16 COSMO-RS-derived descriptors into four chemically interpretable dimensions explaining 86.7% of the total variance. Persistence analysis confirmed component stability, revealing two key factors: PC1 (global solvation propensity, i.e., the overall capacity of the solvent to stabilize solutes through all interaction types) and PC2 (specific interaction complementarity, i.e., the degree of matching between solute and solvent hydrogen-bonding/polarity features). K-means clustering identified four distinct solubility regimes: high-solubility DES-optimized systems (Cluster 1), reliable moderate performers (Cluster 0), intermediate candidates for optimization (Cluster 3), and fundamentally challenging combinations (Cluster 2). Comparative analysis demonstrated choline chloride’s broad utility while revealing specialized roles for menthol and betaine in specific chemical spaces. Case studies of Sulfasalazine and Caffeine illustrated how multi-cluster distributions guide formulation strategies, distinguishing precision-requiring from forgiving compounds. This taxonomy provides formulation scientists with a rational framework for DES selection, emphasizing aqueous modification, HBD and HBA diversity, and balanced solvation-interaction optimization. The integrated PCA-clustering approach transforms DES development from trial-and-error screening to targeted design, offering fundamental insights into solubility mechanisms while accelerating sustainable pharmaceutical formulation. Full article

Background: To repurpose carbutamide (CBT), a discontinued sulfonylurea-class anti-diabetic drug, as an anti-inflammatory bowel disease (IBD) drug, CBT azo-linked with salicylic acid (CAA) was designed and synthesized as a colon-specific prodrug to co-release CBT and mesalazine (5-ASA) selectively in the large intestine. Methods: CAA exhibited reduced lipophilicity and decreased transintestinal transport compared to CBT, as shown in an ex vivo experiment using isolated rat jejunal segments. It also underwent cleavage into CBT and 5-ASA when incubated with cecal contents of rats. Additionally, oral administration of CAA and Sulfasalazine (SSZ), a colon-specific prodrug of 5-ASA currently used for IBD treatment, resulted in similar levels of 5-ASA accumulation in the rat cecal region. Results: In a dinitrobenzene sulfonic acid-triggered colitis model in rats, CAA produced a more pronounced improvement in colon injury and inflammation than SSZ. Furthermore, rectal co-administration of CBT and 5-ASA conferred enhanced protective outcomes compared to monotherapy with either agent alone, suggesting a combined anticolitic action. The two drugs also jointly suppressed valacyclovir uptake via peptide transporter 1 (PepT1) in the distal colon, supporting PepT1 as a target contributing to their combined anticolitic effect. Unlike CBT, which significantly reduced blood glucose following oral administration, equimolar administration of CAA did not alter glycemic levels, consistent with reduced systemic exposure to CBT. Conclusions: In conclusion, CAA functions as a colon-specific mutual prodrug that surpasses SSZ in anticolitic performance while minimizing hypoglycemia risk, thus facilitating the repurposing of CBT as a treatment for IBD. Full article

Background/Objectives: Probenecid (PBN) is a uricosuric agent that facilitates the excretion of uric acid and is used to treat gout. Here, a colon-targeted prodrug of PBN was designed to facilitate repositioning as a treatment for inflammatory bowel disease (IBD). Methods: The carboxylic group in PBN was amide-conjugated with the amine groups of acidic amino acids to yield aspartic acid-conjugated PBN (PBN-AA) and glutamic acid-conjugated PBN (PBN-GA). Conjugation with amino acids increased the hydrophilicity of PBN and decreased cell permeability across the Caco-2 cell monolayer. While remaining intact in buffers (pH 1.2, 6.8) and in the small intestinal contents of rats, the conjugates were cleaved to release PBN from the cecal contents of rats, with a significant difference in the maximal conversion percentage between PBN-AA (12%) and PBN-GA (74%). Results: Upon oral gavage, PBN-GA accumulated a much greater amount of PBN in the cecum than PBN alone, thus verifying the in vitro colon specificity of PBN-GA. Oral PBN-GA enhanced the anticolitis effectiveness in dinitrobenzene sulfonic acid-induced rat colitis and limited the systemic absorption of PBN, thus reducing the risk of systemic adverse effects ascribed to PBN. Moreover, PBN-GA therapeutically surpassed sulfasalazine, a currently used anti-IBD drug, in rat colitis. Conclusions: These results suggest that amide conjugation with GA can be used to design a colon-targeting prodrug for PBN. Colon-targeted PBN may not only enhance therapeutic effectiveness but also improve the safety of PBN repositioned for the treatment of IBD and may be a pharmacological alternative for current small-molecule anti-IBD drugs with low efficacy or serious adverse effects with long-term use. Full article

Introduction: In hemoglobinopathies, the amount of globin synthesis in hemoglobin (Hb) or its structure is altered. Clinical features are related to the rate and kind of structural aberrations. The heterozygous form of the Lepore syndrome resembles minor thalassemia both clinically and hematologically. On electrophoresis, abnormal Hb Lepore fractions are found at a rate of 5–15%, with a mildly higher percentage of HbF and lower HbA. In general, Hb Lepore heterozygotes are asymptomatic. Case presentation: A 32-year-old male was admitted to our hospital with complaints of pain and swelling in multiple large joints and high-grade fever for 11 days. His past history was unremarkable; one of his sisters had the β-thalassemia trait. On physical examination, he was moderately anemic, with mild hepatomegaly and normal spleen; both knees and ankles were tender and swollen. Laboratory showed mild microcytic hypochromic anemia with variables similar to the thalassemia trait and signs of inflammation with very high CRP, serum ferritin, and leukocytosis. Blood sugars were increased. Hb electrophoresis showed an abnormal pattern with mild elevation in HbS, normal Hb F, mild reduction in HbA, and high HbA2, compatible with heterozygosity for the Hb Lepore beta chain variant. He was initially diagnosed with diabetes (treated with insulin) and sepsis from unknown origin, but fever and joint pains did not respond to NSAIDs or antibiotics. He had very good response on high-dose methylprednisolone. Undifferentiated arthritis was diagnosed in the patient with Hb Lepore, and he was treated with oral prednisolone and sulfasalazine (SSZ). At follow up, the patient was doing well. He refused further investigations and did not allow testing on his family members. In summary: Hb Lepore is a rare hemoglobinopathy linked to thalassemia, which may manifest with musculoskeletal problems. Our patient with the Hb Lepore trait presented with undifferentiated polyarthritis and fever, but in our case, a causal relationship remains unclear. This is one of the first adult cases of Hb Lepore in Bangladesh and the first with arthritis of unknown origin. The prevalence of Hb Lepore in Bangladesh is unknown. Full article