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PloS One 2024This study investigated the protective effect of water-soluble propolis (WSP) on colonic tissues in ulcerative colitis (UC) and the role of the protein kinase C -...
Propolis alleviates ulcerative colitis injury by inhibiting the protein kinase C - transient receptor potential cation channel subfamily V member 1 - calcitonin gene-related peptide/substance P (PKC-TRPV1-CGRP/SP) signaling axis.
This study investigated the protective effect of water-soluble propolis (WSP) on colonic tissues in ulcerative colitis (UC) and the role of the protein kinase C - transient receptor potential cation channel subfamily V member 1 - calcitonin gene-related peptide/substance P (PKC-TRPV1-CGRP/SP) signaling pathway. Male SD rats were divided into a control group, a UC model group, various WSP groups (Low-WSP, Medium-WSP, and High-WSP) with UC, and a salazosulfapyridine (SASP) positive control group with UC. After UC was established, the WSP and SASP groups were treated with WSP or SASP, respectively, for 7 d. Each day, body weight measurements were obtained, and the disease activity index (DAI) was recorded by observing fecal characteristics and blood in the stool. After the experiment, hematoxylin and eosin (HE) colonic tissue staining was performed to observe pathological changes, western blotting and immunohistochemistry were performed to detect PKC, TRPV1, CGRP, and SP expression in colonic tissues, and laser confocal microscopy was performed to observe the fluorescence colocalization of PKC/TRPV1, TRPV1/CGRP, and TRPV1/SP. HE staining showed significant colonic tissue structure disruption and inflammatory infiltration in the UC group. Western blotting and immunohistochemistry showed that the expression of PKC, TRPV1, CGRP, and SP in the colonic tissues of the UC group increased significantly compared with that of the control group. Compared with the UC group, the expression of PKC, TRPV1, CGRP, and SP in colonic tissues was significantly reduced in the High-WSP, Medium-WSP, and SASP groups. Immunofluorescence showed the colocalized expression of PKC/TRPV1, TRPV1/CGRP, and TRPV1/SP proteins in the colon tissue of the UC group was significantly reduced after WSP and SASP interventions compared with that of the control group. The results suggest that the mechanism of UC alleviation by propolis may inhibit the PKC-TRPV1-CGRP/SP signaling pathway and the release of inflammatory mediators, thus alleviating inflammation.
Topics: Rats; Male; Animals; Colitis, Ulcerative; Calcitonin Gene-Related Peptide; Substance P; Propolis; Protein Kinase C; Rats, Sprague-Dawley; Signal Transduction; Sulfasalazine; Transient Receptor Potential Channels; TRPV Cation Channels
PubMed: 38206948
DOI: 10.1371/journal.pone.0294169 -
Heliyon Jan 2024The interaction between sulfasalazine (SSZ) through different functional groups and poly (lactic acid) (PLA) in the chloroform phase was investigated in this study using...
Theoretical and experimental studies on sulfasalazine interactions with poly (lactic acid): Impact of hydrogen bonding and charge transfer interactions on molecular structure, electronic and optical properties.
The interaction between sulfasalazine (SSZ) through different functional groups and poly (lactic acid) (PLA) in the chloroform phase was investigated in this study using density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. The binding energy and thermodynamic parameters show that the hydrogen double bond interaction between SSZ and PLA in state I (-0.71 eV) is stronger than in states II (-0.64 eV) and III (-0.51 eV). The SSZ and PLA interaction results in an enhanced dipole moment, greater solubility, and more negative values for Gibbs free energy (ΔGsolv) and energy gap (Eg). Considerable changes in absorption peaks of SSZ and PLA indicate surface adsorption of the drug (SSZ) into the carrier (PLA) in UV-Vis spectra. Theoretical UV-Vis analysis demonstrates SSZ interaction with PLA happens in the ultraviolet region with a maximum absorption peak at 380 nm, which is close to experimental UV-Vis analysis. The experimental spectra showed minimal variations in the maximum absorption wavelength, with respect to theoretical calculations. The presence of SSZ was found to cause a modification in the structure of PLA, as evidenced by both experimental and theoretical Infrared (IR) spectra.
PubMed: 38205338
DOI: 10.1016/j.heliyon.2023.e23813 -
Cureus Dec 2023Ankylosing spondylitis (AS) is an inflammatory spondyloarthropathy that involves the sacroiliac joints and the axial skeleton. Sulfasalazine's efficacy in treating the...
INTRODUCTION
Ankylosing spondylitis (AS) is an inflammatory spondyloarthropathy that involves the sacroiliac joints and the axial skeleton. Sulfasalazine's efficacy in treating the axial symptoms of AS has been a subject of controversy.
METHODS
This prospective observational study recruited AS patients and categorized them into two groups: the first group had AS for less than or equal to four years and the second group had AS for more than four years. Erythrocytic sedimentation rate (ESR) and C-reactive protein (CRP) levels were recorded at baseline and at six-month follow-up. Disease severity was assessed using the ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) score, and Bath ankylosing spondylitis functional index (BASFI) score.
RESULTS
A total of 33 patients diagnosed with AS were recruited in this study, mostly males (88%) and within 21-30 years of age. ESR and CRP values were measured at baseline and at six months post-treatment with sulfasalazine. Mean ESR and mean CRP values showed a statistically significant reduction of 43.5% (p=0.001) and 58.45% (p=0.0012) respectively, at the 6-month follow-up. Four patients (12.12%) reported gastrointestinal intolerance. The mean reduction in the ASDAS score was 24% (p=0.002), the BASDAI score was 40.08% (p=0.001), and the BASFI score was 39.54% (p=0.01). Additionally, the duration of symptoms did not appear to influence with efficacy of sulfasalazine.
DISCUSSION
Sulfasalazine is a safe alternative therapy for patients with AS who cannot afford biologics, due to its reasonable short-term efficacy, good tolerability, cost-effective nature, and low incidence of adverse effects.
PubMed: 38179353
DOI: 10.7759/cureus.49978 -
Marine Drugs Dec 2023A mathematical concept, n-tuples are originally applied to medicinal chemistry, especially with the creation of scaffold diversity inspired by the hybridisation of...
A mathematical concept, n-tuples are originally applied to medicinal chemistry, especially with the creation of scaffold diversity inspired by the hybridisation of different commercial drugs with cytarabine, a synthetic arabinonucleoside derived from two marine natural products, spongouridine and spongothymidine. The new methodology explores the virtual chemical-factorial combination of different commercial drugs (immunosuppressant, antibiotic, antiemetic, anti-inflammatory, and anticancer) with the anticancer drug cytarabine. Real chemical combinations were designed and synthesised for 8-duples, obtaining a small representative library of interesting organic molecules to be biologically tested as proof of concept. The synthesised library contains classical molecular properties regarding the Lipinski rules and/or beyond rules of five (bRo5) and is represented by the covalent combination of the anticancer drug cytarabine with ibuprofen, flurbiprofen, folic acid, sulfasalazine, ciprofloxacin, bortezomib, and methotrexate. The insertion of specific nomenclature could be implemented into artificial intelligence algorithms in order to enhance the efficiency of drug-hunting programs. The novel methodology has proven useful for the straightforward synthesis of most of the theoretically proposed duples and, in principle, could be extended to any other central drug.
Topics: Cytarabine; Artificial Intelligence; Antineoplastic Agents
PubMed: 38132958
DOI: 10.3390/md21120637 -
Heliyon Nov 2023Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum. The disease is characterized by oxidative stress and severe...
INTRODUCTION
Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum. The disease is characterized by oxidative stress and severe inflammation. Research has shown the anti-oxidative and anti-inflammatory effects induced by consuming the and . The present study aimed to evaluate the effect of treatment with together with on healing, inflammation, and oxidative stress in the course of experimental colitis in rats.
METHODS
A total number of 50 male rats were selected and randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with a 4 % acetic acid solution. Four days after the colitis induction, the rats were orally treated for the next 4 days with saline or a combination of A. arabica and O. basilicum (1000 mg/kg) or sulfasalazine (100 mg/kg).
RESULTS
Acetic acid-induced colitis increased the colon's macroscopic and histopathological damage scores; increased colon levels of MDA (Malondialdehyde), MPO (Myeloperoxidase), TNF-α (Tissue necrosis factor α), IL6 (Interleukin 6), and IL17 (Interleukin 17); and decreased SOD (Superoxide Dismutase), GPx (Glutathione Peroxidase), and IL10 (Interleukin 10) levels in the treated rats compared with the control group (P < 0.001). Overall, a combination of and reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, and MDA, MPO, TNF-α, IL6 (P < 0.001), and IL17 (P < 0.01) levels of the colon. Furthermore, it increased SOD, GPx, and IL10 levels compared to the colitis group (P < 0.01).
CONCLUSION
and have improving effects on UC by reducing inflammation and oxidative stress.
PubMed: 38058645
DOI: 10.1016/j.heliyon.2023.e22355 -
Frontiers in Medicine 2023The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial...
INTRODUCTION
The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.
METHODS
Information on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.
RESULTS
The median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: , and . The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab ( = 4) and sarilumab ( = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.
CONCLUSION
The treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.
PubMed: 38034538
DOI: 10.3389/fmed.2023.1257045 -
Journal of Medicine and Life Aug 2023Ulcerative colitis is a chronic inflammatory disease with high mortality and morbidity worldwide. It causes inflammation in the lining of the colon, resulting in several...
Ulcerative colitis is a chronic inflammatory disease with high mortality and morbidity worldwide. It causes inflammation in the lining of the colon, resulting in several symptoms that negatively impact the quality of life. Unfortunately, there is currently no known cure for this condition. Therefore, it is crucial to explore alternative treatment approaches. This research aimed to investigate the anti-inflammatory and antioxidative effects of a combination therapy involving Sulfasalazine+Ezetimibe compared to Sulfasalazine alone in a rat model of ulcerative colitis. Forty adult rats were divided into four groups for this study. The groups consisted of a control group (negative control), an acetic acid group (positive control), an acetic acid+Sulfasalazine (100 mg/kg per day) group, and an acetic acid+Sulfasalazine (50 mg/kg)+Ezetimibe (5 mg/kg) group. Rats were treated for one week, and colitis was induced by administering 2 ml of 4% (v/v) acetic acid inter-rectally. After sacrifice, the colonic tissue homogenate was analyzed for several markers, including proinflammatory cytokines (TNF-α, IL-1β, NF-κB), oxidative stress markers (malondialdehyde, myeloperoxidase), and adhesive molecule markers (E-selectin, ICAM-1). Sulfasalazine and the combination of Sulfasalazine+Ezetimibe significantly reduced the colonic levels of TNF-α, IL-1β, NF-κB, MDA, and E-selectin in the homogenate. However, the combination therapy of Sulfasalazine and Ezetimibe demonstrated a superior effect.
Topics: Rats; Animals; Sulfasalazine; Colitis, Ulcerative; E-Selectin; NF-kappa B; Tumor Necrosis Factor-alpha; Quality of Life; Colitis; Colon; Biomarkers; Acetates
PubMed: 38024826
DOI: 10.25122/jml-2023-0194 -
Cureus Oct 2023Oromandibular dystonia is a focal dystonia characterized by involuntary movements of the jaw, oropharynx, lips, and tongue. The diagnosis of oromandibular dystonia is...
Oromandibular dystonia is a focal dystonia characterized by involuntary movements of the jaw, oropharynx, lips, and tongue. The diagnosis of oromandibular dystonia is clinical and can be complex. For effective treatment, it is essential to understand its underlying etiology. A 70-year-old man was referred to our center with a diagnosis of Meige's syndrome, which had been present for five and a half years, for receiving botulinum toxin-A (BoNT-A) injections. Upon physical examination, he exhibited oromandibular dystonia, with a score of 177 points on the Oromandibular Dystonia Rating Scale (OMDRS). He had a history of taking methotrexate for six years, as he was diagnosed with psoriatic arthritis during that time. The possibility of methotrexate-induced dystonia was considered. A switch from methotrexate to sulfasalazine was initiated. Subsequently, the patient showed progressive improvement in his symptoms, as reflected by an OMDRS score of 103 points. After eight weeks, the medical team decided to supplement the treatment with BoNT-A injections, resulting in an OMDRS score of 75. While there is currently no definitive evidence linking the use of methotrexate to the development of dystonia, it is advisable to consider oromandibular dystonia as a potential side effect of methotrexate until more robust evidence becomes available.
PubMed: 38022297
DOI: 10.7759/cureus.47248 -
BMC Chemistry Nov 2023The improvement of the solubility of sulfasalazine in physiological media was the major aim of this study. Accordingly, BNNT inspected as a notable candidate for the...
Interaction of sulfasalazine with outer surface of boron-nitride nanotube as a drug carrier in aqueous solution: insights from quantum mechanics and Monte Carlo simulation.
The improvement of the solubility of sulfasalazine in physiological media was the major aim of this study. Accordingly, BNNT inspected as a notable candidate for the carriage of this drug in aqueous media. For this purpose, four possible interactions of two tautomer of sulfasalazine with (9,0) boron-nitride nanotube were considered in aqueous media. The compounds were optimized in gas phase using density functional calculations. Solvation free energies and association free energies of the optimized structures were then studied by Monte Carlo simulation and perturbation method in water environment. Outcomes of quantum mechanical calculations presented that interaction of keto form of sulfasalazine produce the most stable complexes with boron-nitride nanotube in gas phase. Simulation results revealed that electrostatic interactions play a vital role in the intermolecular interaction energies after binding of drug and nanotube in aqueous solution. Results of association free energy calculations indicated that complexes of both two sulfasalazine tautomers (keto and enol) and nanotube were stable in solution. Computed solvation free energies in water showed that the interaction with boron-nitride nanotube significantly improved the solubility of sulfasalazine, which could improve its in vivo bioavailability.
PubMed: 38017542
DOI: 10.1186/s13065-023-01088-w -
BMC Infectious Diseases Nov 2023The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the...
Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR].
INTRODUCTION
The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs).
METHODS
Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients' treatment regimens are initially based on drug resistance profiles and patient's preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions.
DISCUSSION
Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations.
TRAIL REGISTRATION
Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.
Topics: Humans; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Clinical Protocols; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38012543
DOI: 10.1186/s12879-023-08644-8