TP53 mutations are linked to poor prognoses in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), indicating that specific p53 target genes may contribute to drug resistance. Although the impact of specific genetic alterations on drug sensitivity has been reported in BCP-ALL, the effects of TP53 mutations on sensitivity to individual agents remain poorly defined in the clinical setting because of the use of combination chemotherapy regimens. In the present study, we addressed this issue through two complementary analyses using a large panel of BCP-ALL cell lines. Initially, 30 cell lines harboring TP53 mutations demonstrated significantly greater resistance to daunorubicin (DNR), mafosfamide (MAF; an active analog of cyclophosphamide), 6-mercaptopurine (6-MP), and prednisolone compared to 46 cell lines without mutations. Second, 11 CRISPR/Cas9-mediated TP53-knockout sublines derived from cell lines with wild-type TP53 recapitulated resistance to DNR, MAF, and 6-MP, as well as to vincristine (VCR) and cytarabine (Ara-C). Consistent with these findings, re-evaluation of genome-wide CRISPR screening datasets revealed significant enrichment of TP53 gRNAs in cells treated with DNR, MAF, 6-MP, Ara-C, and VCR. Furthermore, transcriptomic and proteomic analyses of p53 target genes in the two cell line models, along with re-evaluation of genome-wide CRISPR screening datasets, identified BAX, BBC3, and FDXR as key p53 target genes associated with multidrug resistance. These results highlight the potential value of targeting these p53 downstream pathways to improve outcomes in TP53-mutated BCP-ALL cases.

To compare the therapeutic efficacy of a thioredoxin domain-containing protein 5 (TXNDC5) monoclonal antibody (mAb) against prednisolone and sulfasalazine in DSS-induced IBD-related intestinal fibrosis mouse models. A total of 48 C57BL/6 mice were randomly divided into four model groups (Group A-D, 12 animals per group), while seven extra mice were assigned to the blank control group. Intestinal fibrosis was induced in mice of Groups A to D via recurrent administration of 2% DSS solution. On day 26 post-modeling, five mice from each model group were sacrificed to validate model success, and the leftover animals were treated with corresponding drugs or saline for 14 successive days. Multiple detection indexes were assessed in this study, consisting of body weight, DAI score, colonic morphological features, serum levels of transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α), collagen deposition level as well as colonic TXNDC5 expression. One-way ANOVA coupled with Tukey's post hoc test was applied for all statistical analyses. The TXNDC5 mAb group presented better weight restoration and earlier DAI remission. It obtained longer colon length, lower colon weight, decreased serum inflammatory cytokines and milder collagen accumulation relative to the two conventional drug groups (all P < 0.05). Meanwhile, TXNDC5 mRNA and protein expression were significantly downregulated in the mAb group compared with prednisolone and sulfasalazine groups. No statistical difference was found between the two traditional medication groups. At the experimental doses adopted in the present study, TXNDC5 mAb showed more pronounced anti-inflammatory and anti-fibrotic effects than prednisolone in DSS-induced mice. However, due to the potentially sub-therapeutic sulfasalazine dose, its comparative superiority over sulfasalazine cannot be established from the current data. These findings should be considered preliminary and hypothesis-generating, requiring further validation in optimized experimental settings.

Lyell's syndrome (LS) is a severe drug-induced cutaneous adverse reaction, associated with high morbidity and mortality. We present the case of a 41-year-old male who, after the use of topical medications, developed fever, maculopapular lesions, ocular and mucosal involvement, with affectation of more than 30% of the body surface area. Cutaneous biopsy ruled out other pathologies. Management included systemic methylprednisolone, aluminum subacetate, topical mupirocin, ophthalmic prednisolone, and ophthalmic hypromellose, with a favorable outcome and without complications. This case highlights the importance of considering topical medications as possible triggers for LS, as well as the need for early diagnosis and timely management. Early identification and a multidisciplinary therapeutic approach are fundamental to improve clinical outcomes and reduce the morbidity and mortality associated with this entity.

Prolonged glucocorticoid (GC) therapy is frequently complicated by secondary vitamin D3 deficiency, which acts as a potential pathogenetic modulator of GC-induced neurotoxicity. This study investigated the role of disturbed calcium homeostasis and neuroinflammation in GC-induced brain damage and evaluated the protective potential of vitamin D3 (VD3, cholecalciferol). Female Wistar rats (n = 54) were divided into control, GC-treated (prednisolone, 5 mg/kg/day, 30 days, per os), and VD3-correction (1000 IU/kg/day, concurrent with GC) groups. Analysis of calcium-binding protein levels (calbindin-D28K, S100B, osteocalcin) and neurospecific markers (NF-L, MBP, GFAP) was performed using ELISA, Western blot, and confocal microscopy. Prolonged prednisolone administration caused significant systemic and local 25(OH)D3 deficiency, accompanied by a twofold reduction in osteocalcin protein content and elevated calbindin-D28K levels. Reactive astrogliosis, characterized by increased GFAP+ cell counts and S100B content, occurred alongside decline in NG2+ oligodendrocyte precursors. Significant neuroinflammation was recorded: TNF-α levels rose 1.62-fold in the cortex and 1.65-fold in the hippocampus, while IL-1β increased 2.66-fold and 2.40-fold, respectively. Furthermore, markedly increased serum levels of NF-L, S100B, GFAP, and MBP indicated alterations consistent with blood-brain barrier dysfunction and neuro-glial disintegration. VD3 therapy effectively restored serum markers (osteocalcin, S100B, MBP), suppressed astrocyte reactivity, and normalized cortical cytokine levels while partially replenishing NG2+ cell pool. Although its impact on hippocampal inflammation was limited, these findings demonstrate that maintaining adequate VD3 levels is paramount for preserving CNS integrity by stabilizing calcium buffering and suppressing neuroinflammation. Our results emphasize clinical importance of monitoring VD3 status to mitigate risk of glucocorticoid-induced neurotoxicity and associated neurological complications.

Primary pulmonary lymphoma (PPL) is rare malignancies, accounting for less than 1% of primary lung malignancies and extranodal lymphomas. Primary pulmonary follicular lymphoma is an uncommon subtype of PPL. Herein, we report the case of a 29-year-old immunocompitent man who presented with persistent pulmonary infiltrations despite appropriate antibiotic treatment for presumed pneumonia. Computed tomography (CT) of chest revealed multifocal consolidations with surrounding ground-glass opacities, predominantly involving the peripheral and lower lung zones, along with multiple mediastinal lymphadenopathy. Brochoscopy with bronchoalveolar lavage cultures and microbiological investigation, including tests for bacterial, mycobacterial, and fungal pathogens, were all negative. Histological examination of transbronchial biopsy (TBBx) demonstrated atypical B-cell lymphoproliferation, Immunohistochemistry was positive for CD20, CD10, BCL2, and BCL6, while AE1/AE3 and thyroid transcription factor-1 (TTF1) highlighted reactive pneumocytes. No evidence of any extrathoracic manifestration is comfirmimg the diagnosis of primary pulmonary follicular lymphoma. The patient was treated with rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP), resulting in significant clinical and radiographic improvement. This case highlights the diagnostic challenge of primary pulmonary follicular lymphoma, which may mimic chronic pulmonary infection, particularly in young immunocompetent patients. Persistent pulmonary consolidations despite appropriate antimicrobial therapy should prompt consideration of early tissue diagnosis to exclude an underlying malignancy.

A 59-year-old Japanese man developed pruritus and swelling of the right dorsal foot after weeding his garden in a crouching position for approximately one hour. Over a period of five months, the swelling, as well as skin induration, progressed unilaterally from the right thigh to the lower leg and dorsal foot. Laboratory tests, including eosinophil fraction and inflammatory markers, were within normal limits, and computed tomography showed no evidence of deep vein thrombosis or malignancy. A full-thickness biopsy including the fascia revealed marked fascial thickening with fibrosis of the subcutaneous connective tissue, and perivascular lymphocytic inflammatory infiltrates without conspicuous eosinophils, leading to a diagnosis of eosinophilic fasciitis. Oral prednisolone (30 mg/day) resulted in gradual improvement. To the best of our knowledge, 11 cases of unilateral eosinophilic fasciitis have been reported (three in Japan and eight outside Japan). Including the present case (total 12), six cases lacked peripheral blood eosinophilia, and seven lacked significant eosinophilic infiltration in tissue; five showed neither. Eosinophilic fasciitis should be considered even in the absence of eosinophilia; therefore, early full-thickness biopsy including the fascia is essential for accurate diagnosis.

Glucocorticoids can inhibit the pulsatile secretion of Gonadotropin-releasing-hormone (GnRH). Therefore, if the body's own cortisol is permanently elevated, as is the case in Cushing's syndrome or exogenous treatment with glucocorticoids, gonadotropin secretion can be weakened. Additionally, women's menstrual cycle and fertility can be affected due to hypothyroidism. Anti-Müllerian hormone (AMH) produced by granulosa cells is described as a fertility marker. The aim of this study was to investigate the effects of Cushing's syndrome or exogenous glucocorticoids and hypothyroidism on the reproductive cycle and AMH-levels in bitches. Gynaecological examinations and AMH measurements were performed in 42 dogs of different breeds. Twenty-eight received cortisone (prednisolone), ranged from 0.1 to 2.1 mg/kg orally once per day, 6 had Cushing's syndrome and 8 hypothyroidisms. Twenty-eight healthy female dogs served as a control group. Seventeen bitches with cortisone treatment showed prolonged anestrus, 8 of them returned to heat after discontinuation or reduction of the dosage. Two bitches experienced delayed onset of puberty. Two bitches with Cushing's syndrome showed prolonged anestrus, too, but none with hypothyroidism exhibited cycle alterations. The AMH values between the different groups did not differ (p = 0.14). The AMH levels of all 21 bitches with changes in their estrous cycle did not differ from those of the bitches without changes (p = 0.47). Cortisone treatment can suppress estrus in bitches. Cushing's syndrome may lead to prolonged anestrus, while hypothyroidism seems to have no effect on the estrous cycle, but a larger experimental group is required to assess these effects. Bitches with cycle alterations showed no change of AMH level.

Eculizumab, a monoclonal antibody targeting complement C5, has been shown to be effective when administered within 2-4 days of disease onset in children with severe acute poststreptococcal glomerulonephritis (APSGN). However, since APSGN typically follows a self-limited clinical course in most patients, the optimal timing and latest feasible time window for eculizumab initiation in APSGN remain undefined. A 9-year-old girl presented with gross haematuria, oliguria, and renal dysfunction 9 days after the onset of vomiting and abdominal pain. Laboratory tests showed a positive anti-streptolysin O titre, decreased serum complement C3 levels, massive proteinuria, and stage 3 acute kidney injury. Following high-dose methylprednisolone and continuous renal replacement therapy, her serum C3 levels recovered to normal range, yet oliguria and renal impairment persisted two weeks after disease onset. Since serum complement membrane attack complex (C5b-9) remained substantially elevated, eculizumab was initiated at a delayed time point compared with previous reports, yielding a rapid improvement in renal function. Kidney biopsy performed post-treatment with eculizumab revealed focal proliferative glomerulonephritis, accompanied by acute tubular injury. At the 6-month follow-up, except for haematuria detected by dipstick urinalysis, the patient had normal renal function, serum complement C3 levels and negative urinary protein. No severe adverse events occurred. We present a case of APSGN with persistent renal dysfunction and excessive complement activation 2 weeks after glucocorticoid therapy, who achieved substantial clinical remission upon eculizumab administration. Our observation suggests eculizumab may be an effective rescue intervention for persistent renal dysfunction in severe APSGN driven by excessive complement activation.

Autoimmune hepatitis (AIH) is an autoimmune liver disease characterized by immune-mediated hepatocellular destruction. This review provides a comprehensive update on the changes in the clinical landscape of and advancements in therapy for AIH up to 2026. Recent epidemiological data indicate a significant increase in both the incidence and prevalence of AIH worldwide, emphasizing potential shifts in environmental triggers and heightened disease awareness. Diagnosing AIH remains intricate owing to atypical manifestations; however, the newly updated 2025 European Association for the Study of the Liver clinical practice guidelines introduce refined simplified diagnostic criteria that incorporate contemporary laboratory platforms and international pathology standards to enhance real-world sensitivity. Immunosuppressive therapy continues to be the cornerstone of management. Corticosteroids remain the standard first-line treatment, while the upfront combination of prednisolone and mycophenolate mofetil is increasingly recommended alongside conventional azathioprine regimens. Achieving a complete biochemical response-defined as the normalization of transaminases and immunoglobulin G within 6 to 12 months-has emerged as a powerful, universally recognized surrogate endpoint for long-term prognosis, strongly predicting lower liver-related mortality and transplantation rates across both Western and Asian cohorts. Furthermore, this review addresses complex clinical entities, including drug-induced autoimmune-like hepatitis secondary to novel immunotherapies or vaccinations, and the phenotypic continuum of the primary biliary cholangitis-AIH overlap syndrome. Finally, we highlight the clinical utility of emerging, highly specific diagnostic biomarkers, such as anti-docking protein 2 antibodies-a promising candidate for seronegative cases, pending external multicenter validation-and outline essential directions for future AIH research.