Cytotoxic and genotoxic stress transiently increase the contribution of platelet-biased hematopoietic stem cells to platelet production.

Chemotherapy-induced alopecia (CIA) is a major unresolved adverse effect in clinical oncology. We have previously shown that the Sonic hedgehog (Shh) signaling pathway is targeted by cyclophosphamide (CYP) treatment, but the detailed mechanism by which this chemotherapy drug induces alopecia still remains largely unknown. To answer this question, in the present study, we used Shh-GFP+/- mice and analyzed Shh-expressing cells (Shh+ cells) in hair follicles at different times post-CYP treatment. Through flow cytometry assays, we showed that Shh+ cells decreased significantly after CYP treatment. To investigate the molecular events involved in this decrease, we carried out gene set enrichment analysis of RNA sequencing data of Shh+ cells, which revealed that the expression levels of most Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway-related genes were upregulated compared to the controls. Furthermore, through a chromatin immunoprecipitation assay, we showed that STAT1 could bind to the promoter of the Shh gene during CIA in hair follicles and the binding strength increased upon CYP treatment. Treatment with JAK inhibitors also rescued hair loss and upregulated Shh expression in mice with CIA, further supporting the role of the JAK/STAT1 signaling pathway in the regulation of Shh during CIA. Taken together, our results provide new insights into the molecular mechanisms of CIA.

Alkylating agents, particularly cyclophosphamide (CY), are known for their high toxicity, which can lead to iatrogenic premature ovarian insufficiency (POI) and infertility in young cancer survivors. Currently, effective prevention and treatment strategies remain limited. Given that chemotherapy induces cellular senescence, we investigated the therapeutic potential of dasatinib (D) and quercetin (Q), a senolytic combination known to eliminate senescent cells. Using a CY-induced murine model of ovarian injury, we found that CY treatment increased the accumulation of senescent cells in the ovaries. The resulting senescence-associated secretory phenotype (SASP) led to a deterioration of the ovarian microenvironment, characterized by increased follicular atresia and a decline in follicle quantity, ultimately culminating in POI. Our findings demonstrate that DQ therapy effectively mitigated CY-induced damage by clearing senescent cells and reducing SASP secretion. Clinically, DQ administration restored sex hormone levels and regularity of the estrous cycle, resulting in an overall increase in follicle numbers across all developmental stages. Furthermore, DQ treatment significantly normalized estrous cyclicity, restoring regular cycles in 60% of the CY+DQ mice compared to only ~15% in the CY-alone group (p<0.0001). RNA sequencing analysis revealed that DQ treatment upregulated Pagr1a, a gene associated with extraembryonic development, while downregulating genes involved in senescence induction (Itgb3, Wnt10b, Vegfa) and immune function (A2m, Ccl21d). These results suggest that senescent cells drive CY-induced ovarian damage and that DQ represents a promising therapeutic strategy for preserving the ovarian reserve and endocrine function in female cancer patients.

Objective: To assess the effects of Co-enzyme Q10 supplementation on the histology of the spleen in immunocompromised female Albino Wistar rats. Methodology: A quasi-experimental study was conducted between July 2021 and December 2021 at the Anatomy Department of Isra University Hyderabad. Forty female adult Albino Wistar rats (n=10/group) were included in the present study, divided into 4 groups where A was kept as vehicle control, B as experimental group, C as pre-treatment group, and D was kept as post-treatment. All drugs were administered through the intraperitoneal route. On Day 09, animals were sacrificed through cervical dislocation and dissected. Spleen was carefully dissected from each animal and washed thoroughly with distilled water, and tissue was fixed in 10% formalin and processed for light microscopy. Results: On the histopathological findings, the moderate and severe white pulp atrophy was significantly higher in group B (p-0.001). All the animals of control group A were without haemorrhagic findings, while mild haemorrhage was seen in 3 animals of group b, 3 animals in group C and 3 animals of group D. Moderate haemorrhage was seen in 5 animals of group B and 2 animals of group D, while severe haemorrhage was seen only in 2 animals of group B. The moderate and severe haemorrhage was significantly higher in group B (p-0.001). Furthermore, the moderate and severe necrosis was significantly higher in group B (p-0.001). Conclusion: The histological changes, including white pulp atrophy, haemorrhage, and necrosis, were most frequently observed in the spleens of immunosuppressed female rats treated with cyclophosphamide. A significant cytoprotective effect of Coenzyme Q10 was noted in these rats, as spleen histology showed marked improvement in those treated with Coenzyme Q10 alongside cyclophosphamide, regardless of whether Coenzyme Q10 was administered before or after the start of cyclophosphamide treatment.

BackgroundAggressive multiple sclerosis (MS) causes early, rapid accumulation of disability with frequent and severe relapses, incomplete recovery from relapses, and/or high T2 lesion burden. Severe relapses are typically treated with high-dose IV corticosteroids followed by plasmapheresis. Patients who do not respond to initial treatment lack universally accepted second-line options. Cyclophosphamide is used in clinical practice for MS patients that do not respond to initial relapse therapy. Despite its use, there is no conclusive data demonstrating its efficacy.ObjectiveTo review the UBC MS clinic experience in using cyclophosphamide as a rescue therapy for MS patients.MethodsWe screened the UBC MS Clinic pharmacy database to identify MS patients followed at the UBC MS clinic that received cyclophosphamide between June 2009 and June 2024 for retrospective chart review.ResultsThe median EDSS score prior to cyclophosphamide therapy was 6 (range 2.5–9). Thirteen out of 23 patients had an improvement in EDSS, including 6/23 with a ≥3 EDSS numerical improvement.ConclusionRescue cyclophosphamide treatment was associated with improvement in EDSS in MS patients with a relapsing course. Despite the availability of high-efficacy DMTs, this cohort shows there may be a role for cyclophosphamide in the context of severe relapses.

Cyclophosphamide (CYP) may through its toxic metabolite, acrolein, induce hemorrhagic cystitis and bladder hyperactivity. Previous studies demonstrated intra-iliac arterial administration of adipose derived mesenchymal stem cells (ADSC)-derived microvesicles with less immune response and adverse effects than ADSC itself may confer anti-oxidative stress and anti-inflammatory potential to improve bladder dysfunction. We explored whether ADSC-derived microvesicles may prevent CYP-induced bladder cystitis and overactivity. Female Wistar rats were divided into control (Con), CYP (Cy), CYP+microvesicles (CyM), and microvesicles treated control (CoM) groups. Con rats were intraperitoneally treated with saline, while the Cy rats were induced by intraperitoneally administered CYP (100 mg/kg body weight). We injected ADSC-derived microvesicles at the dosage of 15 μg/ml via intra-iliac artery to the rats with or without CYP treatment. We measured the responses of transcystometrogram, pathology, expression of muscarinic receptors (M3) and purinergic receptors (P2X7), pyroptosis related Caspase 1 and IL-1β, xCT/Gpx4 related ferroptosis by western blot in CYP-treated bladders. Wire myography of the urinary bladder was determined. ADSC-derived microvesicles effectively decreased micturition frequency (overactivity), inflammation and fibrosis in CyM rats versus Cy rats. ADSC-derived microvesicles efficiently downregulated P2X7 and M3 receptor expression, Caspase 1/IL-1β mediated pyroptosis, xCT/Gpx4 regulated ferroptosis and restored Bcl-2/HO-1 mediated antioxidant defense mechanisms in CYP-induced cystitis. The pathologic results also displayed the effective reduction of bladder immune cell infiltration (inflammation) and fibrosis, and the preservation of the integrity in the urothelium by the treatment of ADSC-derived microvesicles. ADSC-derived microvesicles can ameliorate CYP-induced bladder overactivity, inflammation, fibrosis, ferroptosis and pyroptosis.

Cyclophosphamide is a therapeutic agent with an extensive clinical application. It is used in treating acute and chronic leukaemia, lymphomas, multiple myeloma, rheumatoid arthritis and in preparation for bone marrow transplantation. However, cyclophosphamide has numerous organ toxicities that have limited its clinical use. The study aimed to investigate the ameliorative effect of the methanol extract of Tectona grandis leaf on cyclophosphamide-induced cardiotoxicity. Twenty female Wistar rats were randomly divided into four groups (n=5). Cardiac toxicity was induced in Wistar rats by administering cyclophosphamide 50 mg/kg BW IP daily for three days. Tectona grandis leaf extract (200 and 400 mg/kg) was orally administered immediately after cyclophosphamide treatment on the fourth day for 21 days. The control group received only feed and water. After the 21-day treatment, the rats were euthanized under anesthesia to obtain blood for biochemical analysis. Histopathological evaluation was also conducted. Data was analyzed using the statistical package GraphPad Prism version 8.0.2. Analysis of variance (ANOVA) and post hoc test were carried out. Cyclophosphamide administration significantly elevated (p&lt;0.05) the troponin level and activities of creatine kinase and lactate dehydrogenase compared with the control. Additionally, the cyclophosphamide alone-treated group showed elevated levels of malondialdehyde, reduced activities of antioxidant enzymes- superoxide dismutase, catalase and glutathione peroxidase and abnormal changes in lipid profile status compared with the control and other treatment groups. Treatment with methanol T. grandis leaf extract (MTGLE) reversed the changes by significantly (p&lt;0.05) reducing the levels of troponin and malondialdehyde, increasing the activities of creatine kinase, lactate dehydrogenase, superoxide dismutase, catalase and glutathione peroxidase while restoring the lipid profile of cyclophosphamide- induced rats. The result of the histopathological examination showed an improvement in the cardiac histo- architecture of MTGLE-treated groups, which supports the findings of the biochemical investigation. This suggests that Tectona grandis may possess a promising ameliorative effect against cyclophosphamide- induced cardiotoxicity in rats.

Abstract Background: In the KEYNOTE-522 study (NCT03036488), neoadjuvant pembrolizumab (pembro) plus chemotherapy (chemo) followed by adjuvant pembro plus chemo significantly improved pathological complete response (pCR), event-free survival, and OS compared with placebo (pbo) plus chemo in participants (pts) with early-stage TNBC. Following neoadjuvant therapy, the estimated treatment difference in pCR for pembro plus chemo vs pbo plus chemo was 13.6% (95% CI, 5.4%‒21.8%; P &amp;lt; 0.001) at the first interim analysis (N=602). Although pCR provides a definitive indicator of neoadjuvant treatment success, other measures, such as RECIST v1.1 and functional tumor volume (FTV), may offer an earlier signal of therapeutic activity. This prespecified exploratory analysis evaluated associations of pCR with ORR at different time points per MRI by RECIST v1.1 and FTV by blinded independent central review. Methods: Pts with previously untreated TNBC (stage T1c N1-N2 or T2-T4 N0-N2) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or pbo, each with 4 cycles of paclitaxel plus carboplatin (treatment 1) then with 4 cycles of doxorubicin or epirubicin plus cyclophosphamide (treatment 2). After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence/unacceptable toxicity. Breast MRI was performed for consenting pts at screening and after neoadjuvant treatments 1 and 2. Responders were defined as pts who achieved CR or PR per RECIST v1.1 by blinded independent central radiology review. The subgroup analyses population included the randomized pts who signed MRI consent and had baseline values by central radiology review. Results: At data cutoff (March 23, 2021), MRI subgroup analyses included 162 pts (pembro plus chemo, n = 97; pbo plus chemo, n = 65). After treatment 1, ORR per RECIST v1.1 was 91.8% for pembro plus chemo vs 84.6% for pbo plus chemo, while ORR per MRI FTV was 96.9% vs 93.8%. After treatment 2, ORR per RECIST v1.1 was 82.5% vs 90.8%, and ORR per MRI FTV was 84.5% vs 92.3% for pembro plus chemo and pbo plus chemo, respectively. In the post hoc exploratory analyses for pCR in the MRI subgroup, pCR rate (ypT0/Tis ypN0; 95% CI) was 62.9% (52.5%-72.5%) with pembro plus chemo vs 52.3% (39.5%-64.9%) with pbo plus chemo. Odds ratios (OR) for achieving pCR among pts with ORR per RECIST v1.1 or FTV across all patients (pembro plus chemo and pbo plus chemo combined) are shown in the Table. Conclusions: Across all pts (ie, for pembro plus chemo and pbo plus chemo combined), the odds of achieving pCR were higher among pts who had an objective response per either RECIST v1.1 or FTV. Citation Format: J. Cortés, R. Dent, H. McArthur, L. Pusztai, S. Kümmel, C. Denkert, J. O’Shaughnessy, P. A. Fasching, M. Untch, R. Tarnawaski, M. Mouret-Reynier, S. M. Stemmer, T. Foukakis, J. Boileau, C. Chung, M. Fernandez, J. A. Mejia, F. Beca, S. Hou, P. Schmid. Phase 3 study of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab for early-stage TNBC: KEYNOTE-522 magnetic resonance imaging (MRI) subgroup analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-24.

Locally advanced breast cancer (LABC) is an inoperable breast adenocarcinoma that is commonly treated with neoadjuvant chemotherapy. Neoadjuvant chemotherapy is given to patients as the first step in treatment to reduce tumor size before surgery. However, no biomarkers are currently available to predict early response to chemotherapy. The differential expression of miRNAs between malignant and normal cells from patients with breast cancer reflects tumor dynamics and may reflect an individual's resistance or sensitivity to drugs used in chemotherapy. Ten patients with LABC who responded to chemotherapy, five patients with LABC who did not respond, and three healthy controls were included in this study. This study found that miRNAs miR-214-3p, miR-222-3p, and let-7e-5p indicated a patient's sensitivity to neoadjuvant chemotherapy. Whereas miR-20a-5p, miR-27a-3p, miR-424-5p, miR-152-3p, and miR-195-5p suggested a patient's resistance to it. Therefore, these findings suggest that miRNAs may serve as predictive biomarkers and potential therapeutic targets in the management of breast cancer.

Over 317,000 new cases of breast cancer will be diagnosed in 2025, making it the most diagnosed cancer among women in the United States. Advancements in treatment options such as chemotherapy and radiation have resulted in a 5-year survival rate of 91%. Upwards of 78% of the 4.1million breast cancer survivors currently living in the United States report chemotherapy induced cognitive impairment (CICI), or "chemobrain". CICI defined as an impairment in memory, learning, executive function, and attention following chemotherapy treatment. There is a need for a better understanding of the long-term side effects of these treatments and the impact these may have on the quality of life for these survivors. In this study, we used a translational mouse model to study cognitive decline via intraperitoneal injections of the combination chemotherapy AC-T: Doxorubicin (DOX), Cyclophosphamide (CYP), and Paclitaxel (PTX). Mice underwent behavior tests to assess social memory and anxiety 30 days after the last AC-T injection. AC-T treated mice revealed behavioral deficits in social memory and an increase in anxiety-like behavior. RNA-sequencing and western blot analysis revealed negatively altered expression of transcripts associated with neurogenesis, axonal guidance, neurotransmission, and protein IEGs such as Arc, c-Fos, and Egr-1, respectively. Proteomics indicated increases in inflammatory markers in intestinal tissue, which also coincided with changes in intestinal morphology of AC-T treated mice. The gut microbiota of AC-T treated mice showed became dysbiotic. This study provides a multi-omic overview of the effects of AC-T treatment on cognition and intestinal inflammation and morphology.

This study aimed to evaluate the clinical utility of serum anti-phospholipase A2 receptor (PLA2R) antibodies in assessing clinical features and therapeutic responses in idiopathic membranous nephropathy (IMN). A retrospective analysis was conducted on 99 patients with IMN admitted to Tianjin Medical University General Hospital between August 2023 and April 2024, stratified into seronegative and seropositive groups. Baseline characteristics, biochemical parameters, anti-PLA2R antibody levels, and 3 treatment strategy outcomes were analyzed. Receiver operating characteristic curve analysis assessed the diagnostic accuracy of anti-PLA2R antibodies. Results revealed statistically significant differences in albumin and urine total protein (U-TP) between the seronegative and seropositive groups (P < .05). Compared with the seropositive group, patients in the seronegative group had a better prognosis. Compared with the tacrolimus plus methylprednisolone and cyclophosphamide plus methylprednisolone treatment regimens, the recovery of microalbuminuria, U-TP, albumin, and anti-PLA2R was greatest after treatment with rituximab, and the therapeutic effect was better. Importantly, among these 4 markers, the change in anti-PLA2R was most substantial. The receiver operating characteristic analysis identified an optimal anti-PLA2R cutoff of 15.53 ng/mL, achieving 76.77% sensitivity, 100% specificity, and an area under the curve of 93.3% (P < .001). These findings highlight that rituximab demonstrates substantial clinical value in improving serum albumin levels, reducing U-TP, microalbuminuria, and anti-PLA2R antibody levels in patients with IMN while also underscoring the critical role of anti-PLA2R antibodies in IMN characterization and therapeutic monitoring.

ObjectivesThis study examines the effects of cyclophosphamide, a cancer treatment that also functions as a cytotoxic agent, on the nephrotic system. The extent to which stem cell applications can be effective in preventing nephrotoxicity caused by agents is also a subject of investigation. The extent to which the nephrotoxic effects detected in the animal model treated with cyclophosphamide can be prevented by stem cell application will be investigated.Material and MethodsA total of 18 Sprague Dawley rats were included in the study, divided into 3 groups. Group 1 consisted of the control group, which received intraperitoneal (IP) saline injection. Group 2-cyclophosphamide and Group 3-cyclophosphamide + stem cell was administered IP cyclophosphamide (50 mg/kg cyclophosphamide on the first day and then 8 mg/kg intraperitoneally for 14 days) to create a nephrotoxicity model. Group 3-cyclophosphamide + stem cell also received weekly hUCMSC 10*6 IP for 2 weeks. 4 weeks after the treatment, the animals were euthanized, their kidney tissues were histopathologically and immunohistochemically evaluated, and their blood values were biochemically evaluated.ResultIn histopathological examination, glomerulosclerosis and tubular damage were seen the most in Group 2, and this difference was found to be statistically significant (p<0.001 and p<0.01). However, no statistically significant difference was observed in terms of inflammation in the kidney tissues (p=0.068). No significant change was observed in the biochemically evaluated BUN, creatinine, or urea levels in all three groups (p<0.8; p<0.141; p<0.8).ConclusionIn light of the current information, human Umbilical Cord Mesenchymal Stem Cell (hUC-MCS) has been demonstrated to reduce the nephrotoxicity caused by cyclophosphamide given for cytotoxic purposes on the kidney and exhibit induced renal regeneration. Our findings create new hope for the use of stem cell therapies in the field of kidney diseases.

PurposeCyclophosphamide is a commonly used chemotherapeutic agent in hematopoietic stem cell transplantation (HSCT), but its use can lead to adverse effects such as hemorrhagic cystitis (HC) and electrolyte disturbances, including hyponatremia. While standard hydration protocols are used to mitigate these risks, the optimal regimen remains unclear. This study explores the impact of a restrictive hydration regimen on HC incidence and electrolyte imbalances in patients undergoing high-dose cyclophosphamide treatment as part of HSCT conditioning.MethodsA retrospective cohort study was conducted at Amsterdam UMC, including patients who received high-dose cyclophosphamide as part of HSCT between 2016 and 2024. Patients were grouped based on hydration protocols: an original regimen (5 L of NaCl 0.45%/dextrose 2.5% per day) and a new restrictive regimen (1.5 L/m2/day of 0.65% NaCl). The primary endpoint was the incidence of HC, while secondary endpoints included sodium and potassium changes, fluid overload (measured by furosemide use), and clinical outcomes.ResultsHC occurred in 10/386 (2.6%) patients in the original protocol and 1/69 (1.4%) in the restrictive protocol (odds ratio [95% confidence interval]: 0.55 [0.03–2.96], p = 0.57). Clinically relevant hyponatremia was less common with the restrictive regimen (1.4%) than with the original protocol (4.4%), though the difference was not significant (p = 0.27). On the other hand, patients receiving the restrictive regimen showed more clinically relevant hypokalemia (8.7% vs 5.9%, p = 0.28). Fluid overload, as indicated by furosemide use, was lower in the restrictive group albeit not statistically significant.ConclusionIn this retrospective single-center cohort, we did not observe a higher incidence of HC or electrolyte imbalances with a restrictive hydration regimen compared to the original regimen.

The objective: to analyze the effectiveness and safety of non-drug and drug therapy of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the prospects for the use of new drugs. Materials and methods. In order to achieve the task, an in-depth analysis of scientific articles on the treatment of patients with RA-ILD in journals which are indexed in the Web of Science, Google Scholar, SCOPUS, MEDLINE, UpToDate, ResearchGate databases was carried out. The search in scientometric databases was conducted using the following keywords: “Rheumatoid arthritis-associated interstitial lung disease”, “Pathogenesis”, “Treatment”, “DMARD”, “Biologic agents”, “Anti-fibrotics”, “Methotrexate”, “Glucocorticoids”, “Azathioprine”, “Mycophenolate Mofetil”, “Leflunomide”, “Sulfasalazine”, “Cyclophosphamide”, “Anti-TNF agents”, “Rituximab”, “Abatacept”, “Tacrolimus”, “Janus kinase inhibitors”, “Pirfenidone”, “Phosphodiesterase 4 inhibitors”. Results. RА is a chronic systemic inflammatory disease typically characterized by symmetrical erosive polyarthritis and a variety of extra-articular manifestations, including ILD. The treatment of ILD is currently challenging due to the high infectious risk and possible pulmonary iatrogenic toxicity of some drugs, as well as the lack of randomized clinical trials. The prevalence of RA in the European population is 0.5-1%, with the cumulative incidence of RA-ILD estimated at 18.7%. The 10-year mortality rate for RA-ILD can be as high as 60.1%, prompting researchers to determine the new approaches to the treatment of this pathology, analyzing traditional anti-inflammatory drugs and new agents with antifibrotic effects. This review of the literature highlights the current state of knowledge regarding the genetic determinants of the development and pathogenesis of RA-ILD, as well as possible pathogenetically based approaches to its treatment. Systematic randomized trials on the treatment of this pathology have not yet been conducted, despite the rather contradictory data on the impact of first-line RA therapy drugs on the course of RA-ILD. This review article identifies non-drug treatment options and analyzes the efficacy and safety of various pharmacological drugs for the treatment of RA, including glucocorticoids (GCs), synthetic disease-modifying antirheumatic drugs (DMARDs) and biologics, as well as some new drugs with antifibrotic effects. Conclusions. The management of RA-ILD is a complex and comprehensive process that includes non-drug and drug treatment strategies. This review article provides current information on the management of patients with RA-ILD and approaches to pharmacological therapy. Non-pharmacological treatments include respiratory rehabilitation, psychosocial support, and pneumococcal and influenza vaccination. GCs, mycophenolate mofetil, abatacept, and Janus kinase inhibitors may be effective and safe in the treatment of RA-ILD, while leflunomide, sulfasalazine, and cyclophosphamide are contraindicated in the treatment of patients with RA-ILD. Rituximab, pirfenidone, and phosphodiesterase 4 inhibitors are promising but understudied.

Cyclophosphamide (CP), a classical alkylating chemotherapeutic drug, has significant genotoxic effect but its use is restricted due to safety concerns. In the present study, we investigated a protective effect of Syzygium aromaticum (clove) ethanolic extract against CP-induced chromosomal damage in Swiss albino mice. Thirty male mice were distributed among five groups (n = 6): control, clove extract only (500 mg/kg), CP only (20 mg/kg intraperitoneally), and two post-treatment groups, receiving CP followed by oral clove extract at 400 mg/kg and 500 mg/kg for seven days. Chromosomal anomalies and micronucleus formation were assessed in bone marrow cells. CP treatment significantly increased structural chromosomal anomalies from 2.24 ± 1.01 (control) to 18.72 ± 0.05 (p &lt; 0.05) and numerical aberrations from 3.62 ± 0.03 to 15.68 ± 0.02 (p &lt; 0.05). Micronucleated polychromatic erythrocytes (MnPCEs) increased 9.9-fold from 1.38 ± 0.02% to 13.63 ± 1.01% (p&lt;0.05). Post-treatment with 400 mg/kg clove extract reduced structural and numerical aberrations to 10.94 ± 3.01 and 11.03 ± 0.03, respectively, representing 42% and 30% reductions in these aberrations. The 500 mg/kg dose achieved greater protection, reducing structural aberrations by 74% (4.92 ± 0.03) and numerical aberrations by 68% (5.03 ± 0.05), approaching control values. MnPCE frequency decreased to 8.84 ± 1.02% (35% reduction) and 4.98 ± 0.05% (63% reduction) at 400 mg/kg and 500 mg/kg doses, respectively. The dose-dependent genoprotective effects are attributed to the high eugenol content and phenolic compounds in cloves, which possess antioxidant properties. These findings suggest that clove extract may be a promising natural chemoprotective agent for mitigating CP-induced genotoxicity, warranting further investigation for potential clinical applications.

Objective: To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM). Methods: A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children's hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ² test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results: Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity (OR=13.26, 95%CI 1.37-128.29) and elevated FAR (OR=1.90, 95%CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95%CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions: The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

ObjectiveTo determine the demographic and clinical characteristics associated with use of the EuroLupus or modified National Institutes of Health (NIH) cyclophosphamide (CYC) regimen for treatment of lupus nephritis (LN) at North American pediatric centers.MethodsA retrospective cohort study was conducted at 11 North American centers. Patients <22 years of age with active LN treated with CYC using the EuroLupus or NIH regimen between July 2014 and June 2021 were included. Data were extracted via electronic medical record review. Demographic and clinical characteristics were compared at CYC initiation. A multivariable generalized estimating equation with logit link was fit to model EuroLupus use. An exchangeable correlation structure was used to account for correlation within centers. Independent variables were chosen using elastic net regression.ResultsThe cohort consisted of 191 patients (85 EuroLupus, 106 NIH) with a median age of 15.3 years at CYC initiation. In multivariable analysis, characteristics significantly associated with EuroLupus regimen use (vs NIH regimen use) included more recent year of CYC initiation, longer disease duration, Hispanic ethnicity and Asian race (as compared to Black), previous CYC treatment, renal impairment (dialysis or mild kidney impairment), and absence of neuropsychiatric involvement.ConclusionFor children and young adults with LN requiring CYC, use of the EuroLupus regimen increased over time and is associated with demographic and clinical factors such as race or Hispanic ethnicity, renal impairment, and absence of neuropsychiatric involvement. The differences in regimen use with severe renal impairment and neuropsychiatric lupus highlight areas for future study in CYC dosing.

Objective Systemic lupus erythematosus (SLE) is associated with increased cancer risk. However, the patterns of cancer incidence remain unclear. This study aimed to evaluate the cancer risk in patients with SLE. Method This population-based cohort study identified 24 241 patients with newly diagnosed SLE between 2004 and 2020 using Korean National Health Insurance Service data. Patients were followed up until cancer diagnosis, death, or December 2021. Standardized incidence ratios (SIRs) were calculated to compare cancer risk between patients with SLE and the general population. Subgroup analyses were performed based on the age at diagnosis, follow-up duration, and use of immunosuppressive agents. Results Patients with SLE had higher risks of overall [SIR 3.3, 95% confidence interval (CI) 3.2–3.4], solid (SIR 3.1, 95% CI 3.0–3.2), and haematological (SIR 9.8, 95% CI 8.9–10.9) cancers compared with the general population. Among solid cancers, liver cancer had the highest risk, followed by ovarian cancer. The relative cancer risk peaked among patients aged 20–39 years (SIR 4.9, 95% CI 4.6–5.2) and during the first year after diagnosis (SIR 4.7, 95% CI 4.3–5.1). The SIRs for haematological, cervical, and lung cancers in cyclophosphamide-treated patients were higher than those for the corresponding cancers in the overall SLE population. Conclusion Patients with SLE have increased cancer risk compared with the general population. Increased relative cancer risk is associated with younger age, first year post-diagnosis, and cyclophosphamide treatment.

Radiotherapy and cyclophosphamide (CYP) treatment can adversely affect various organs, including the liver and pancreas. In addition to hepatic toxicity, CYP and/or ionizing gamma radiation (R) may impact the exocrine and endocrine functions of the pancreas. This study aims to determine whether sodium thiosulfate (STS) can protect male rats against CYP and/or R-induced damage to the pancreas and liver. Sixty-four rats were divided into eight groups, with STS administered for 14 days prior to CYP and/or R treatment. Enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as insulin and glucose levels, were assessed. Amylase and lipase concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and malondialdehyde (MDA) levels were determined to evaluate lipid peroxidation. Glutathione content (GSH), glutathione-S-transferase (GST) activity, and reactive oxygen species (ROS) were quantified. Gene expression of extracellular signal-regulated kinase (Erk-1) and c-Jun N-terminal kinase (JNK) was analyzed using real-time quantitative polymerase chain reaction (qPCR). Histopathological examination and immunohistochemical staining with anti-nuclear factor erythroid 2-related factor 2 (anti-Nrf2) antibodies were performed. STS treatment increased GSH, GST, and insulin levels while reducing ROS, MDA, glucose, amylase, and lipase levels. Furthermore, the STS treatment significantly downregulated mitogen-activated protein kinases (MAPKs) such as ERK and JNK Additionally, STS administration increased Nrf2 levels in both pancreatic and hepatic tissues while minimizing pathological changes. These findings suggest that STS may hold promise as a protective agent against CYP and/or R-induced liver and pancreatic damage. The ability of STS to enhance antioxidant defenses, reduce oxidative stress, modulate signaling pathways, and preserve tissue integrity suggests its therapeutic potential in mitigating the detrimental effects of these damaging conditions by inhibiting the MAPK, ERK, and JNK signaling pathways.

Background/Objectives: The role of daratumumab, lenalidomide, and dexamethasone (DRd) in autologous stem cell transplantation (ASCT)-eligible patients with multiple myeloma (MM) after first-line bortezomib, cyclophosphamide, and dexamethasone (VCd) treatment is not yet established. Methods: We retrospectively evaluated ASCT-eligible patients with MM who received second-line therapy with DRd after initial induction therapy with VCd between 2017 and 2023 (salvage group). For comparison, patients who successfully underwent per-protocol treatment with VCd induction, followed by ASCT during the same period, were selected (control group). Results: Eight patients with a median age of 61 years (range, 36–68 years) were included in the salvage group. After a median of 5 DRd cycles, the best response was partial response (PR) in two patients (25%) and a very good partial response (VGPR) in six (75%). All patients underwent ASCT, resulting in PR in one (13%), VGPR in four (50%), and stringent complete response in three (38%). Measurable residual disease (MRD) assessed using multicolor flow cytometry was negative in four patients (50%). The controls included thirteen patients with a median age of 60 years (range, 44–64 years). While most patients in both groups received various post-ASCT therapies, the post-ASCT 2-year time to the next treatment rate was slightly better in the salvage group than in the control group (88% vs. 49%, p = 0.089). However, hypogammaglobulinemia was more common in the salvage group (75% vs. 15%, p = 0.018). Conclusions: This small case series suggests that DRd is promising for ASCT-eligible patients with MM after VCd failure.