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Cisplatin resistance in ovarian cancer cells is mainly apoptosis resistant. Although other types of programmed cell death are highly involved in chemoresistance, which type can overcome cisplatin resistance remains unclear. The present study observed that cisplatin-sensitive SKOV3 cells and cisplatin-resistant SKOV3/DDP cells had different levels of sensitivity to sulfasalazine (SAS). The present study aimed to investigate the effect of SAS on necroptosis under the same inhibition rate in these two types of cells. Necroptosis inhibitor Necrostatin-1 (Nec-1) attenuated SAS-induced SKOV3/DDP cytotoxicity. SAS decreased SKOV3/DDP cells survival rate, accompanied by decreased cell adhesion and spreading. SAS treatment activated necrosome formation in SKOV3/DDP cells, suggesting the possibility of necroptosis. p62/sequestosome-1 (SQSTM1) protein expression levels were also increased over the same time period. The transfection of small interfering (si)-p62 could decrease the ratios of phosphorylated (p)-receptor-interacting serine/threonine kinase 1 (RIP1)/RIP1, p-receptor-interacting serine/threonine kinase 3 (RIP3)/RIP3 and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in SKOV3/DDP cells. Under the si-p62 condition, there was no increase in the rate of cell survival in Nec-1 and SAS combination group compared with SAS. The zinc finger domain deletion of p62/SQSTM1 effectively decreased the expression levels of necroptosis-related p-proteins. Collectively, certain drugs were able to induce necroptosis in SKOV3/DDP, while p62/RIP1/RIP3/MLKL was associated with the induction of necroptosis and with increasing the sensitivity of cisplatin-resistant ovarian cancer cells, which provided evidence for potential as a therapeutic target for overcoming resistance. [ABSTRACT FROM AUTHOR]

By summarizing and analyzing the diagnostic and treatment process of a case with atypical Stevens–Johnson syndrome (SJS) characterized by mucosal ulcerations of the pharynx and larynx, and reviewing related literature, we would like to remind that in the presence of unexplained mucosal lesions, atypical SJS should not be ignored. [ABSTRACT FROM AUTHOR]

Backgrounds: Glioblastoma (GBM) is a highly aggressive brain cancer associated with poor prognosis, primarily attributed to its profound invasive characteristics. Glutamate is the main cause of invasion, and invasion is promoted by system Xc− (cystine/glutamate antiporter), which is highly expressed in GBM. To date, no studies have examined the relationship between invasion and the specific downregulation of system Xc− (xCT or SLC7A11) using shRNA in GBM. Objective: We aimed to determine the effect of a specific knockdown system, Xc−, in GBM using short hairpin RNA (shRNA) rather than pharmacological approaches. Results: Invasion was inhibited in GBM cells treated with sulfasalazine, a system Xc− inhibitor. Our experiments validated a reduction in extracellular glutamate concentration following sulfasalazine treatment, without affecting GBM proliferation or calcium response. However, the efficacy of pharmacological methods is hindered by nonspecific effects and the prevalence of multiple side effects. Therefore, we specifically targeted the system Xc− molecule through shRNA. Downregulation using shRNA demonstrated decreased invasion and extracellular glutamate levels, without affecting the calcium response and proliferation. Conclusion: The targeted inhibition of system Xc− using shRNA yields a notable reduction in GBM invasion. [ABSTRACT FROM AUTHOR]

Background: Sulfasalazine is a widely used anti-inflammatory medication for treating autoimmune disorders such as ulcerative colitis (UC), Crohn's disease, and rheumatoid arthritis. However, its safety profile has not been systematically evaluated in real-world settings. By analyzing the FDA Adverse Event Reporting System (FAERS) database, we identified risk signals associated with adverse reactions to sulfasalazine, offering valuable insights for clinical decisionmaking and risk management. Methods: Reports of adverse events (AEs) associated with sulfasalazine, covering the period from Q1 2004 to Q4 2023, were extracted from the FAERS database. Detailed case information was aggregated to assess demographic characteristics. The associations between sulfasalazine and adverse events were evaluated using the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Results: We extracted 7,156 adverse event reports from the FAERS database where sulfasalazine was identified as the "Primary Suspect (PS)" drug. Using disproportionality analysis, we identified 101 preferred terms (PT) related to sulfasalazine across 24 organ systems. Notable adverse reactions consistent with the drug's labeling were observed, including Stevens-Johnson syndrome, agranulocytosis, eosinophilic pneumonia, and crystalluria. Additionally, novel positive signals not previously documented in the drug label were identified, including acute febrile neutrophilic dermatosis, aseptic meningitis, glomerulonephritis, and hepatosplenic T-cell lymphoma. Conclusion: Most of the adverse reaction findings in this study are consistent with previous clinical research, and we have also identified new potential AEs associated with sulfasalazine. These findings provide valuable insights for the safety monitoring and clinical application of sulfasalazine. [ABSTRACT FROM AUTHOR]

Sulfasalazine, a relatively well-tolerated, disease-modifying anti-rheumatoid drug has been reported to be associated with hepatic and cutaneous adverse events, in addition to its common adverse effect profile. The present case reports a reaction cascade involving hepatic, ocular, and cutaneous reaction in a female patient secondary to her sulfasalazine use. The report highlights the importance of multidisciplinary teamwork in the treatment and adverse event management in these cases, to help patients with better and safer treatment outcomes.

Abstract Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction characterized by cutaneous rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and life-threatening organ dysfunctions. We describe the case of a 26 year old patient admitted to the Emergency Department for DRESS syndrome after sulfasalazine treatment for rheumatoid arthritis in the right knee. Whole body computer tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly, massive ascites and severe hepatic cytolysis. Serology results for Epstein-Barr Virus (EBV), influenza, measles, rubella, hepatitis A and B were negative. The histologic analysis of skin, lymph node and bone marrow biopsies could not indicate a classical Hodgkin’s Disease or iatrogenic immunodeficiency/EBV-associated lymphoproliferative disorder (LPD), Hodgkin type. The relatively small caliber of the CD30 + immunoreactive blastoid cells in the lymph nodes suggested reactive immunoblasts rather than Hodgkin cells. The morphologic aspects of the lymph node biopsies with predominance of T-cells were compatible with the diagnosis of a sulfasalazine-induced DRESS syndrome as the patient had a high RegiSCAR score for DRESS. [DRESS Syndrome Foundation: Diagnosis and Treatment. (2023)] The patient’s complex clinical course, marked by two hospital admissions, highlights the challenges in diagnosing and managing DRESS. This case underscores the need for individualized care, close patient monitoring, and further research to better understand DRESS’s underlying mechanisms and optimal therapeutic strategies.

Objective To investigate the effects of baicalein on T helper cells (Th) 1/2, obestatin and 5-hydroxytryptamine (5-HT) in rats with ulcerative colitis. Methods Forty SPF grade male SD rats were randomly divided into normal group (group N), model group (group M), sulfasalazine group (group S), and baicalein group (group B), with 10 rats in each group. The ulcerative colitis models were established in group M, S and B by trinitrobenzenesulfonic acid. After successful modeling, 0.3 g/kg sulfasalazine was given to group S by gavage, and 50 mg/kg baicalein was given to group B by gavage. Group N and group M were given the same volume of normal saline by gavage at the same time. The disease activity index (DAI) score and colon mucosa damage index (CMDI) score of rats were evaluated, and the pathological morphology of colon tissue was detected by hematoxylin and eosin staining. The protein expression of Th1 cytokine interferon-γ (IFN-γ) and Th2 cytokine interleukin-4 (IL-4) in colon tissues was detected by western blot, and the levels of obestatin and 5-HT in rat serum were detected by ELISA. Results All rats were successfully modeled. The DAI score and CMDI score were significantly increased in group M compared to those in group N (P

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction characterized by cutaneous rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and life-threatening organ dysfunctions. We describe the case of a 26 year old patient admitted to the Emergency Department for DRESS syndrome after sulfasalazine treatment for rheumatoid arthritis in the right knee. Whole body computer tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly, massive ascites and severe hepatic cytolysis. Serology results for Epstein-Barr Virus (EBV), influenza, measles, rubella, hepatitis A and B were negative. The histologic analysis of skin, lymph node and bone marrow biopsies could not indicate a classical Hodgkin's Disease or iatrogenic immunodeficiency/EBV-associated lymphoproliferative disorder (LPD), Hodgkin type. The relatively small caliber of the CD30 + immunoreactive blastoid cells in the lymph nodes suggested reactive immunoblasts rather than Hodgkin cells. The morphologic aspects of the lymph node biopsies with predominance of T-cells were compatible with the diagnosis of a sulfasalazine-induced DRESS syndrome as the patient had a high RegiSCAR score for DRESS. [DRESS Syndrome Foundation: Diagnosis and Treatment. (2023)] The patient's complex clinical course, marked by two hospital admissions, highlights the challenges in diagnosing and managing DRESS. This case underscores the need for individualized care, close patient monitoring, and further research to better understand DRESS's underlying mechanisms and optimal therapeutic strategies. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs and biologic therapy are recognized as standard treatments for ankylosing spondylitis. However, in developing countries like Turkey, the cost of biological treatments can escalate to significant levels. Our study aims to assess the effectiveness of sulfasalazine in axial symptoms, typically considered a secondary treatment in ankylosing spondylitis. We conducted a retrospective analysis of the medical records of patients diagnosed with ankylosing spondylitis. These patients were prescribed sulfasalazine due to the persistence of axial symptoms. After a 3 mo course of sulfasalazine treatment, patients were assessed for changes in sediment and C-reactive protein values, ankylosing spondylitis disease activity score-sedimentation rate and ankylosing spondylitis disease activity score-C-reactive protein values, visual analog scale, bath ankylosing spondylitis disease activity index, and bath ankylosing spondylitis functional index results and morning stiffness durations. In this study, conducted with sulfasalazine treatment, significant improvements were observed across multiple parameters. Morning stiffness duration decreased in 22 patients. Median C-reactive protein levels decreased from 9.99 mg/l (range: 2-53, interquartile range: 12.21) to 6.81 mg/l (range: 1-18, interquartile range: 8.16). Similarly, the median ESR reduced from 20.53 mm/h (range: 4-48, interquartile range: 15.47) to 12.81 mm/h (range: 2-33, interquartile range: 10.57). Ankylosing spondylitis disease activity score-C-reactive protein scores improved from 3.62±0.732 to 2.67±0.93, and ankylosing spondylitis disease activity score-ESR scores improved from 3.54±0.66 to 2.57±0.80. Moreover, patients reported lower visual analogue scale scores, decreasing from 7.39±1.44 to 5.58±1.97. The global disease evaluation by doctors showed a decrease from an average score of 6.33±1.47 (range: 4-10) to 5.11±1.68 (range: 2-8). Ankylosing spondylitis quality of life questionnaire scores improved from 7.92±2.41 to 5.36±2.73. Bath ankylosing spondylitis disease activity index scores decreased from 6.31±1.70 to 4.37±1.76, and bath ankylosing spondylitis functional index scores improved from 3.76±1.98 to 2.79±1.63. These improvements were statistically significant across all measured parameters before and after sulfasalazine treatment (p<0.05). In developing countries like ours, where access to biological drugs which derived from living organisms, can be challenging for economically disadvantaged individuals with limited socioeconomic resources, and where the probability of inducing side effects such as infections, an elevated risk of cancer, and neurological diseases is a concern, sulfasalazine could be considered a more affordable and relatively safer option before resorting to biological treatments for managing ankylosing spondylitis. [ABSTRACT FROM AUTHOR]

Sulfasalazine needs frequent daily dosing and the administration of numerous tablets per day pose challenges to patient compliance, contributing to increased adverse effects and difficulties in disease control. These inconveniences result in less effective treatment for arthritis associated with inflammatory bowel disease i.e. ulcerative colitis etc. To improve drug bioavailability, a delayed-release mechanism that releases the drug at the colon is necessary. To develop and optimize colon-targeted controlled release bilayer tablets coated with pH-dependent polymers. The bilayer tablets containing the immediate release part and sustained release part were developed. The tablets were coated with enteric-coated with Eudragit® S-100 and l -100 to achieve release in the colon. Granule properties and tablets were evaluated. The physicochemical parameters of the tablets were evaluated including, stability study, and drug release in 0.1 N HCl (pH 1.2), pH 6.8 phosphate buffer, pH 7.4 phosphate buffer for 2, 1, and up to 24 h respectively. Radiographic imaging and in vivo pharmacokinetic studies were also done in Rabbits. The bilayer tablets containing immediate and sustained release were successfully developed for the colon targeting. The granule properties were found within the acceptable range indicating good flow properties. The physicochemical properties of the tablets were also found acceptable. The tablets did not show release in 0.1 N HCl and 6.8 phosphate buffer but drug release was found under control in the 7.4 pH buffer. Sulfasalazine coated bilayer tablets were found stable and no significant changes were observed in the stability studies. Based on the X-ray studies, the formulated tablet remained discernible in the stomach, small intestine, and colon for a duration of up to 24 h. Finally, by the 32nd hour, the tablet was no longer visible in the X-ray examination, leading to the conclusion of complete drug release. The drug concentration in plasma remained within the therapeutic range for up to 24 h in vivo. These novel formulations present substantial advantages, providing prolonged targeted drug release and reducing systemic adverse effects. The results suggest promising potential for treating arthritis in Inflammatory bowel disease (IBD) patients, offering a solution to current delivery systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Through molecular recognition, drugs can interact and complex with macromolecules circulating in the body. The serum albumin transport protein, found in several mammals, has several interaction sites where these molecules can be located. The drug sulfasalazine (SSZ) is known in the literature to complex at drug site 1 (DS1) in human serum (HSA) and bovine serum (BSA) proteins. This complexation can be studied using various spectroscopic techniques. With the techniques used in this work, absorption in the ultraviolet and visible regions (UV–Vis) and electronic circular dichroism (ECD), a significant difference was observed in the results involving HSA and BSA. The application of theoretical methodologies, such as TD‐DFT and molecular docking, suggests that the conformation that SSZ assumes in DS1 of the two proteins is different, which exposes it to different amino acid residues and different hydrophobicities. This difference in conformation may be related to the location of DS1 where the drug interacts or to the possibility of SSZ moving in the BSA site, due to its larger size, and moving less freely in HSA. [ABSTRACT FROM AUTHOR]

Introduction: The anti-inflammatory and immunomodulatory properties of tarragon have been noted. Here, we examined the effects of an aqueous extract of the tarragon plant in a rat model of ulcerative colitis. Methods: Ulcerative colitis was induced in Wistar rats using a 2 ml acetic acid (4%) intrarectal enema. Experimental groups received sulfasalazine (2 mg/kg) or tarragon aqueous extract (100 mg/kg) orally for ten consecutive days. After ten days, the animals were euthanized and evaluated for disease activity index (DAI), production of inflammatory and pro-inflammatory mediators in the intestinal tissue. Results: Both the tarragon aqueous extract and sulfasalazine treatments were effective in reducing the disease severity index in experimental ulcerative colitis. Malondialdehyde intensity, nitric oxide level, and myeloperoxidase activity regressed in the colon of animals treated with the tarragon aqueous extract more than in the group treated with sulfasalazine. However, sulfasalazine significantly reduced TNF-α and IL-1 levels compared to the tarragon aqueous extract. There was no statistical difference in IL-6 and PGE2 reduction between the two groups. Conclusion: These findings suggested that the aqueous extract of tarragon may be applied as a natural resource to control ulcerative colitis. [ABSTRACT FROM AUTHOR]

Abstract Using a rat autologous orthotopic liver transplantation (AOLT) model and liver cold ischemia–reperfusion (I/R)-induced intestinal injury, we clarified whether ferroptosis occurred in rat AOLT cold I/R-induced intestinal injury. Additionally, the role and possible mechanism of the ferroptosis activator sulfasalazine (SAS) in intestinal injury-induced ferroptosis in rats with AOLT liver cold I/R were investigated. Sixty specific pathogen free (SPF)-grade adult male Sprague‒Dawley (SD) rats were randomly divided into 5 groups using the random number table method (n = 12). Six rats were randomly selected at 6 hour (h) and 24 h after I/R. Inferior vena cava blood specimens were collected from the portal vein (PV) opening at 6 h and 24 h. The concentrations of serum malondialdehyde (MDA), serum interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Ileal tissue was obtained from the PV opening in rats in each group at 6 h and 24 h, and ileal tissue sections were observed under light microscopy. The contents of intestinal MDA, superoxide dismutase (SOD), glutathione(GSH), glutathione peroxidase 4 (GPX4), and tissue iron were determined by ELISA, and the expression of GPX4 and the cysteine glutamate reverse transporter light chain protein (xCT) was determined by Western blot. The experimental results show that ferroptosis is involved in the pathophysiological process of intestinal injury induced by cold hepatic ischemia–reperfusion in AOLT rats. In addition, SAS (500 mg/kg) may inhibit the cystine/glutamate antiporters (System Xc¯)/GSH/GPX4 signal axis in intestinal injury induced by cold I/R in rat AOLT liver, or iron overload after reperfusion, causing a massive accumulation of L-ROS and activating cellular ferroptosis, further aggravate the intestinal injury.

Key Clinical Message: This case demonstrated the complex pathophysiology of DRESS syndrome presenting with latent human herpes virus infection reactivation due to exposure to sulfasalazine and/or hydroxychloroquine. Patients who do not initially fulfill the diagnostic criteria on admission may evolve and eventually fulfill the criteria. Steroid dose tapering is required to prevent flaring. [ABSTRACT FROM AUTHOR]

Objective: Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA. Methods: CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining. Results: The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53. Conclusions: Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process. [ABSTRACT FROM AUTHOR]

Using a rat autologous orthotopic liver transplantation (AOLT) model and liver cold ischemia–reperfusion (I/R)-induced intestinal injury, we clarified whether ferroptosis occurred in rat AOLT cold I/R-induced intestinal injury. Additionally, the role and possible mechanism of the ferroptosis activator sulfasalazine (SAS) in intestinal injury-induced ferroptosis in rats with AOLT liver cold I/R were investigated. Sixty specific pathogen free (SPF)-grade adult male Sprague‒Dawley (SD) rats were randomly divided into 5 groups using the random number table method (n = 12). Six rats were randomly selected at 6 hour (h) and 24 h after I/R. Inferior vena cava blood specimens were collected from the portal vein (PV) opening at 6 h and 24 h. The concentrations of serum malondialdehyde (MDA), serum interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Ileal tissue was obtained from the PV opening in rats in each group at 6 h and 24 h, and ileal tissue sections were observed under light microscopy. The contents of intestinal MDA, superoxide dismutase (SOD), glutathione(GSH), glutathione peroxidase 4 (GPX4), and tissue iron were determined by ELISA, and the expression of GPX4 and the cysteine glutamate reverse transporter light chain protein (xCT) was determined by Western blot. The experimental results show that ferroptosis is involved in the pathophysiological process of intestinal injury induced by cold hepatic ischemia–reperfusion in AOLT rats. In addition, SAS (500 mg/kg) may inhibit the cystine/glutamate antiporters (System Xc¯)/GSH/GPX4 signal axis in intestinal injury induced by cold I/R in rat AOLT liver, or iron overload after reperfusion, causing a massive accumulation of L-ROS and activating cellular ferroptosis, further aggravate the intestinal injury. [ABSTRACT FROM AUTHOR]

Berberine (BBR) is a compound derived from Chinese herbal medicine, known for its anticancer properties through multiple signaling pathways. However, whether BBR can inhibit tumor growth by participating in ferroptosis remains unconfirmed. In this study, we demonstrated that berberine synergistically inhibited NSCLC in combination with multiple ferroptosis inducers, and this combination synergistically down-regulated the mRNA and protein expression of SLC7A11, GPX4, and NRF2, resulting in ferroptosis accompanied by significant depletion of GSH, and aberrant accumulation of reactive oxygen species and malondialdehyde. In a lung cancer allograft model, the combination treatment exhibited enhanced anticancer effects compared to using either drug alone. Notably, p53 is critical in determining the ferroptosis sensitivity. We found that the combination treatment did not elicit a synergistic anticancer effect in cells with a p53 mutation or with exogenous expression of mutant p53. These findings provide insight into the mechanism by which combination induces ferroptosis and the regulatory role of p53 in this process. It may guide the development of new strategies for treating NSCLC, offering great medical potential for personal diagnosis and treatment.

Liang Fu,1,2,&ast; Wenfei Wang,2,3,&ast; Juan Xiong,4,&ast; Peize Zhang,2 Hui Li,2 Xilin Zhang,5 Hancheng Liang,6 Qianting Yang,2 Zhaoqin Wang,2 Xinchun Chen,3 Guofang Deng,2 Yi Cai,3 Shenjie Tang1 1Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, People’s Republic of China; 2Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People’s Republic of China; 4Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 5Tuberculosis Prevention and Control Department, the Fourth People’s Hospital of Foshan, Foshan, Guangdong, People’s Republic of China; 6Division Two of Tuberculosis Diseases Department, the Sixth People’s Hospital of Dongguan, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shenjie Tang; Yi Cai, Email tangsj1106@hotmail.com; caiyi0113@szu.edu.cnBackground: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB.Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment.Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures.Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.Plain language summary: This study explored a new way to treat a hard-to-treat type of tuberculosis (TB) using a medicine called Sulfasalazine, alongside usual TB treatments. Over 9 months, two groups of patients were given different sets of medicines, one including Sulfasalazine. The results, checked 12 months after treatment, showed that most patients improved, especially those given Sulfasalazine. No one in the Sulfasalazine group died or had their treatment fail, suggesting that Sulfasalazine could be a promising addition to current treatments for this tough-to-treat TB.Keywords: Sulfasalazine, host-directed therapy, pre-extensive drug-resistant tuberculosis, short-course, treatment

Abstract Background Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma. Methods/design GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland. Trial registration NCT05664464. Registered 23 December 2022.

Background and purpose: Ulcerative colitis is a kind of inflammatory bowel disease that involves factors such as genetic predisposition, environmental factors, and disproportionate function of the mucosal immune system in response to intestinal microbial flora. Platelet-rich plasma (PRP) is a blood derivative that has anti-inflammatory and cell-regenerating properties. This study aimed to investigate the effects of PRP on the clinical and inflammatory manifestations in an experimental model of ulcerative colitis. Materials and methods: In this experiment, male BALB/c mice were segregated into four groups, each consisting of 10 mice: the healthy group (negative control), the colitis group without treatment (positive control), the colitis group receiving PRP, and colitis group receiving sulfasalazine. All animals, except for those in the negative control group, were subjected to colitis induction via intrarectal injection of 100 µl of 4% acetic acid. The treatment regimen commenced after the onset of UC symptoms. The mice were euthanasia after 15 days of the last injection, and the disease activity index, as well as the inflammatory factors, were assessed. Results: According to the results, the treatment groups showed a significant decrease in disease activity index, the severity of inflammation, the level of MPO, NO, and IL-1β, IL-6, and TNF-α cytokines expression and production, as well as inflammatory genes COX2 and iNOS expression, compared to the positive control group. Conclusion: The results showed that PRP has favorable anti-inflammatory effects in ulcerative colitis and after additional evaluations, it can be used as an adjunctive treatment along with the drugs used in the treatment of ulcerative colitis patients.

In the landscape of cutaneous adverse drug reactions (cADRs), acute generalized exanthematous pustulosis (AGEP) remains a pertinent dermatological manifestation. This research delineates a clinical presentation consistent with AGEP precipitated by the administration of sulfasalazine in a 68-year-old female. Drawing from the EuroSCAR study's diagnostic parameters, the patient exhibited salient features such as facial erythema and a pervasive papular rash, concomitant with specific hematological perturbations, including leukocytosis and elevated hepatic enzymes. Utilizing the EuroSCAR AGEP validation score, a definitive diagnosis was ascertained, obviating the need for histological confirmation. Subsequent therapeutic interventions facilitated symptomatic resolution, leading to the patient's discharge with a categorical advisory against future sulfasalazine exposure. This elucidation accentuates the causative potential of sulfasalazine in AGEP manifestation and underscores the imperativeness of vigilant diagnosis and timely intervention. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a complex autoimmune disease that affects millions of people worldwide, with a systemic impact. This review explores the role of non-biological conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in its management. We discuss the effectiveness and safety of key csDMARDs such as Nonsteroidal anti-inflammatory drugs, corticosteroids, Hydroxychloroquine, Sulfasalazine, Methotrexate, and Leflunomide in relieving symptoms and slowing the progression of the disease. We also highlight the importance of combination therapy using csDMARDs, supported by clinical studies demonstrating the benefits of various csDMARD combinations. Early intervention with these drugs is emphasized to prevent joint damage, improve clinical symptoms, and enhance patient outcomes. Overall, csDMARDs have proven pivotal in managing RA, providing cost-effective and versatile treatment options. We acknowledge the advantages of biologics but highlight the associated challenges, making the choice between non-biological and biological drugs a personalized decision. This comprehensive overview aims to provide a deeper understanding of RA treatment strategies, contributing to improving the quality of life for patients with this chronic condition. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) have promising prospects as drug nanocarriers but are more limited in biomedical applications due to their poor stability and biocompatibility. To address this issue, sodium alginate–zein (SA-ZN) nanocomposites modified metal–organic framework were developed and used as an effective nanocarrier for sulfasalazine (SSZ) delivery and reduced side effects of, thus improving its bioavailability SSZ. The obtained nanocomposite was structurally and morphologically characterized using different physicochemical techniques including Fourier transform infrared (FTIR), X-ray diffraction (XRD), and field-emission scanning electron microscopy (FESEM). Based on the results, the Zn2(BDC)2(DABCO) MOFs were dispersed in biopolymers. In addition, the antibacterial properties of samples have been studied against Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that the drug-loaded MOF/SA-ZN has a higher antibacterial activity against S. aureus gram-positive bacteria compared to SSZ. The current research provides a promising insight into the fabrication of polymer-modified MOF-based drug delivery platforms and antibacterial agents. [ABSTRACT FROM AUTHOR]

Background and purpose: Ulcerative colitis is a kind of inflammatory bowel disease that involves factors such as genetic predisposition, environmental factors, and disproportionate function of the mucosal immune system in response to intestinal microbial flora. Platelet-rich plasma (PRP) is a blood derivative that has anti-inflammatory and cell-regenerating properties. This study aimed to investigate the effects of PRP on the clinical and inflammatory manifestations in an experimental model of ulcerative colitis. Materials and methods: In this experiment, male BALB/c mice were segregated into four groups, each consisting of 10 mice: the healthy group (negative control), the colitis group without treatment (positive control), the colitis group receiving PRP, and colitis group receiving sulfasalazine. All animals, except for those in the negative control group, were subjected to colitis induction via intrarectal injection of 100 µl of 4% acetic acid. The treatment regimen commenced after the onset of UC symptoms. The mice were euthanasia after 15 days of the last injection, and the disease activity index, as well as the inflammatory factors, were assessed. Results: According to the results, the treatment groups showed a significant decrease in disease activity index, the severity of inflammation, the level of MPO, NO, and IL-1β, IL-6, and TNF-α cytokines expression and production, as well as inflammatory genes COX2 and iNOS expression, compared to the positive control group. Conclusion: The results showed that PRP has favorable anti-inflammatory effects in ulcerative colitis and after additional evaluations, it can be used as an adjunctive treatment along with the drugs used in the treatment of ulcerative colitis patients. [ABSTRACT FROM AUTHOR]

Interleukin 17A (IL‐17A) inhibitors, such as secukinumab, have been widely used as the mainstream treatment for chronic plaque psoriasis; however, cutaneous adverse events have been reported. Here, we report a 43‐year‐old Chinese man who developed herpetiform pemphigus (HP) during secukinumab treatment for his psoriasis. He presented with (1) clinical features of HP, which resembled bullous pemphigoid; histopathological features of intraepidermal blisters, eosinophilic/neutrophilic spongiosis, and liquefactive degeneration of the basal cell layer; (3) positive anti‐desmoglein 1 antibody by enzyme‐linked immunosorbent assay and cell surface IgG reactivity within the epidermis by indirect immunofluorescence assay; and (4) a satisfactory response to salicylazosulfapyridine (sulfasalazine). To the best of our knowledge, this is the first report of the development of HP after the use of secukinumab for psoriasis. [ABSTRACT FROM AUTHOR]

Key Clinical Message This case demonstrated the complex pathophysiology of DRESS syndrome presenting with latent human herpes virus infection reactivation due to exposure to sulfasalazine and/or hydroxychloroquine. Patients who do not initially fulfill the diagnostic criteria on admission may evolve and eventually fulfill the criteria. Steroid dose tapering is required to prevent flaring.