Pro and anti-inflammatory diets as strong epigenetic factors in inflammatory bowel disease

Inflammatory bowel disease(IBD)is the consequence of a complex interplay between environmental factors,like dietary habits,that alter intestinal microbiota in response to luminal antigens in genetically susceptible individuals.Epigenetics represents an auspicious area for the discovery of how environmental factors influence the pathogenesis of inflammation,prognosis,and response to therapy.Consequently,it relates to gene expression control in response to environmental influences.The increasing number of patients with IBD globally is indicative of the negative effects of a food supply rich in trans and saturated fats,refined su-gars,starches and additives,as well as other environmental factors like seden-tarism and excess bodyweight,influencing the promotion of gene expression and increasing DNA hypomethylation in IBD.As many genetic variants are now associated with Crohn's disease(CD),new therapeutic strategies targeting modi-fiable environmental triggers,such as the implementation of an anti-inflammatory diet that involves the removal of potential food antigens,are of growing interest in the current literature.Diet,as a strong epigenetic factor in the pathogenesis of inflammatory disorders like IBD,provides novel insights into the pathophysio-logy of intestinal and extraintestinal inflammatory disorders.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery

BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,alternative therapies are needed to understand the disease and develop better treatments.Laparoscopic anti-reflux surgery(LARS)can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects.Successful LARS improves typical gastroesophageal reflux symptoms in most patients,main-ly by reducing the exposure time to gastric contents in the esophagus.Amelio-ration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.AIM To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.METHODS Of 22 patients with LARS(pre-and post/5.8±3.8 months after LARS)and 25 healthy controls(HCs)were included.All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy,during which esophageal biopsy samples were collected using endoscopic tech-niques.Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.RESULTS Post-LARS samples showed significant increases in proinflammatory cytokines[interleukin(IL)-1β,interferon-γ,C-X-C chemokine ligand 2(CXCL2)],anti-inflammatory cytokines[CC chemokine ligand(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],and homeostatic cytokines(CCL27,CCL20,CCL19,CCL23,C-CL25,CXCL12,migration inhibitory factor)compared to both HCs and pre-LARS samples.CCL17 and CCL21 levels were higher in pre-LARS than in HCs(P<0.05).The mRNA expression levels of AKT1,fibroblast growth factor 2,HRAS,and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS.CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs(P<0.05).CONCLUSION The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium.Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS.The anti-inflam-matory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.

Antibacterial, Anti-Inflammatory and Antioxidant Activities of an ACAZY Herbal Formula Used in Traditional Medicine to Treat Respiratory Infections

ACAZY is a plant formula used in traditional medicine in Burkina Faso to treat respiratory infections. After phytochemical analysis, this study evaluated extracts’ anti-inflammatory, antioxidant and antibacterial properties from the ACAZY recipe. Three extractions, an aqueous macerate (AM), an aqueous decoction (AD) and an hydroethanolic macerate (HEM) of the ACAZY recipe powder were carried out. Phytochemical screening of the extracts was carried out using high-performance thin-layer chromatography (HPTLC) and the determination of phenolic compounds. The anti-inflammatory potential was assessed in vitro using pro-inflammatory enzyme inhibition tests. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and Ferric-reducing antioxidant power (FRAP) antioxidant properties were also determined. The antibacterial activity was evaluated on Staphylococcus aureus and Streptococcus pneumoniae strains. Phytochemical analysis revealed the presence of flavonoids, saponins, tannins, anthracenosids, sterols and triterpenes in the extracts. The extracts inhibited pro-inflammatory enzymes by more than 40% at only 100 µg/mL. The extracts also showed potent antibacterial activity with a minimum inhibitory concentration 1 mg/mL on Staphylococcus aureus and 2 mg/mL on Streptococcus pneumoniae. The extracts in the ACAZY formula have shown anti-inflammatory and antioxidant properties in vitro. The AD also showed an antibacterial activity. This justifies its use in traditional medicine to treat acute respiratory infections.

Safety and in Vivo Anti-Inflammatory Activity of Ethanolic Extract of Ficus umbellata (Vahl.) Leaves

Toxicity is the totality of adverse effects, which can be functional and morphological lesions in a living organism, caused by a substance introduced in relatively high single doses or in small, repeated doses. The aim of this study was to assess the OECD-recommended acute oral toxicity and anti-inflammatory activity of ethanolic extract of Ficus umbellata leaves. Animals were given a single oral dose of 1000, 3000 and 5000 mg/Kg body weight (BW) of the extract. For the anti-inflammatory activity test, rats were given the ethanolic extract of F. umbellata leaves at doses of 100, 300 and 500 mg/Kg or aspirin® at a concentration of 100 mg/Kg PC orally, one hour before injection of 0.05 ml of 1% formalin under the plantar fascia of the rat’s right hind paw. Paw volume measurements were taken one, two and three hours after formalin injection, using an electronic caliper. After 14 days of observation, no deaths were observed in treated rats. The LD50 of ethanolic extract of Ficus umbellata leaf powder is greater than 5000 mg/Kg body weight. This extract has no significant effects on hematological parameters and on the main markers of nephrotoxicity and hepatotoxicity for a single dose of less than 5000 mg/Kg PC. It reduces formalin-induced edema. Evaluation of the percentage inhibition showed that the extract had greater anti-inflammatory activity at 3 hours after the start of the experiment. However, better inhibition of inflammatory oedema of the paw of rats treated with 500 mg/Kg was observed at 5 hours after the start of the experiment, with a percentage inhibition of 69.23 ± 1.02, compared with the reference group treated with aspirin® 100 mg/Kg, which showed an inhibition of 63.50 ± 0.98. These results show that F. umbellata leaves possess anti-inflammatory activity, which would justify their use in traditional African medicine to prevent or treat inflammation.

Crocus sativus L.produces anti-inflammatory effects and regulates the NLRP3–NF-κB pathway

Objective:This study aimed to evaluate the anti-inflammatory effects of petal and stamen extracts of saffron crocus(Crocus sativus)and explore the underlying mechanism.Methods:Local and systemic inflammation models were used to investigate the anti-inflammatory effects of C.sativus.A xyleneinduced inflammation model or lipopolysaccharide(LPS)-induced inflammation model was used in this study.C.sativus petal and stamen extracts were each administered to the mice in the xylene and LPS models by gavage for 14 d at 0.1 and 0.4 g/kg doses,respectively.Enzyme-linked immunosorbent assay(ELISA)was used to measure the concentrations of tumor necrosis factor(TNF)-αand interleukin(IL)-1βin mouse serum.Hematoxylin and eosin(H&E)staining was used to observe the pathological changes in the ear in the xylene-induced inflammation model and in the spleen in the LPS-induced inflammation model.NOD-like receptor thermal protein domain associated protein 3(NLRP3)protein levels within the nuclear factor-kappa B(NF-κB)pathway were assessed using western blotting.RAW264.7 cells were treated with LPS(5μg/mL)and LPS+C.sativus(0.05,0.1,and 0.2 mg/mL)for 24 h,and a Cell Counting Kit-8 was used to measure cell proliferation.Changes in NLRP3 and NF-κB levels were evaluated by western blotting.Results:Petal and stamen extracts of C.sativus attenuated the anti-inflammatory effects in local or systemic inflammatory models and repaired pathological changes in the ear in the xylene-induced inflammation model and spleen in the LPS-induced inflammation model.These extracts also decreased the concentrations of TNF-αand IL-1βin the mouse serum in the LPS-induced inflammation model.C.sativus downregulated NLRP3 protein level through the NF-κB pathway and downregulated LC-3 and BECLIN1 in vivo and in vitro.Carbonyl Cyanide3-ChloroPhenylhydrazone(CCCP)weakened the effects of C.sativus on the NLRP3–NF-κB pathway.Conclusion:C.sativus has anti-inflammatory effects and regulates the NLRP3-NF-κB pathway.

Protective effects of long term antiplatelet and anticoagulant therapy in hospitalized patients with inflammatory bowel disease

BACKGROUND Inflammatory bowel disease(IBD),with its rising prevalence rates is associated with an increased risk of cardiovascular and thromboembolic events.Antiplatelets and/or anticoagulants agents are often prescribed but the literature on the impact of long-term anticoagulation and/or antiplatelet use among patients hospitalized with IBD is scarce.The aim of this study is to assess the outcomes of patients hospitalized with IBD on antiplatelet and/or anticoagulant agents.AIM To investigate the effects of long-term use of antiplatelets/anticoagulants on clinical outcomes in patients hospitalized with IBD.METHODS We conducted a retrospective cohort study using the Nationwide Inpatient Sample database,including all adult IBD patients hospitalized in the United States from 2016 to 2019.Patient cohorts were stratified based on antiplatelet/anticoagulant therapy status.Multivariate regression analysis was done to assess outcomes,adjusting for potential confounders.The primary outcome was mortality,whereas length of stay(LOS),total parenteral nutrition,acute kidney injury,sepsis,shock,gastrointestinal bleeding,need for colonoscopy/sigmoidoscopy,abdominal surgery and total hospitalization charges were secondary outcomes.RESULTS Among 374744 hospitalized IBD patients,antiplatelet or anticoagulant therapy alone was associated with significantly lower in-hospital mortality and reduced healthcare utilization,including shorter LOS and decreased hospitalization costs.Combined therapy was associated with a protective effect on mortality,but did not reach statistical significance.Notably,therapy did not exacerbate disease severity or complications,although higher odds of gastrointestinal bleeding were observed.CONCLUSION Our study highlights the potential benefits of long-term anticoagulation/antiplatelet therapy in hospitalized IBD patients,with improved mortality outcomes and healthcare utilization.While concerns regarding gastrointestinal bleeding exist,the overall safety profile suggests a role for these agents in mitigating thromboembolic risks without exacerbating disease severity.Further research is needed to look at optimal treatment strategies and addressing limitations to guide clinical decision-making in this population.

Roles of Community Pharmacists in Screening and Disseminating of Information about Non-Steroidal Anti-Inflammatory Drugs Risks: Implications for Drug Safety Assessment

Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.

Preprocessing and Efficacy Analysis of Comprehensive Anti-Inflammatory Treatment for Lymphedema in Patients with Irritating Contact Dermatitis

Objective: To explore the pre-treatment and efficacy analysis of comprehensive anti-inflammatory treatment for lymphedema in patients with irritating contact dermatitis. Method: Convenience sampling method was used to observe the skin of 160 patients with upper limb lymphedema admitted to the lymphedema outpatient department of our hospital. They were divided into an observation group (80 cases) and a control group (80 cases), and both groups received a course of comprehensive anti-inflammatory treatment (20 treatments). The control group received routine skin care;On the basis of the control group, the observation group received pre-treatment of the affected limb skin: Laofuzi herbal ointment was applied externally to the prone areas of irritating contact dermatitis (such as the upper arm, inner forearm, and cubital fossa). Result: The incidence of irritating contact dermatitis in the observation group was significantly lower than that in the control group (P 0.05). Patients in the observation group felt significantly better in terms of comfort, skin moisture, and itching relief after being wrapped with low elasticity bandages than those in the control group (P Conclusion: Preventive treatment can effectively reduce the incidence of irritating contact dermatitis, prolong the time of stress treatment, thereby increasing efficacy and improving patient compliance.

Tamanu Oil in Acne Management: Potential Anti-Inflammatory and Wound-Healing Properties for Scar Reduction

Tamanu oil, derived from the nuts of Calophyllum inophyllum, has gained increasing attention for its potential in acne management due to its purported anti-inflammatory and wound-healing properties. This analysis evaluates the efficacy of tamanu oil in acne treatment with a specific focus on its impact on inflammation and scar reduction. The novelty of this research lies in its comprehensive analysis of tamanu oil’s dual mechanism of action: reducing acne-related inflammation and promoting the healing of acne scars. Clinical trials and laboratory analyses were conducted to assess the oil’s effectiveness in diminishing erythema, swelling, and post-acne scarring compared to conventional treatments. Preliminary findings demonstrate that tamanu oil significantly reduces inflammation and accelerates wound healing, potentially offering a promising adjunct or alternative to standard acne therapies. Future research should aim to optimize formulation and application protocols, long-term effects, and comparative therapeutic efficacy with other anti-inflammatory agents. Tamanu oil offers a novel and effective approach to acne management, with potential advantages that go beyond inflammation reduction to include enhanced scar reduction, making it a subject that warrants further investigation.

类风湿性关节炎滑膜病变高频超声表现与Anti-ccp、ESR及CRP的相关性

目的分析类风湿性关节炎(RA)滑膜病变高频超声表现与抗环瓜氨酸肽抗体(Anti-CCP)、红细胞沉降率(ESR)和C反应蛋白(CRP)的相关性,以期为该疾病早期诊断及治疗方案的制定提供更为准确和科学的依据。方法选取2020年1月至2023年3月于大庆龙南医院风湿免疫科住院的治疗前RA患者65例(RA组),另选取同期于本院体检中心行体检的健康者55名(对照组)。比较两组高频超声表现、髌上囊液体厚度、滑膜厚度、滑膜动脉RI及实验室指标(Anti-ccp、ESR及CRP水平),RA组根据Anti-ccp、ESR及CRP阳性标准分为阳性、阴性组,比较Anti-ccp、ESR及CRP阳性及阴性组的髌上囊液体厚度、滑膜厚度、滑膜动脉RI。采用Pearson分析滑膜病变高频超声表现各指标与Anti-ccp、ESR及CRP的相关性。结果对照组膝积液少<4 mm;RA组80%膝积液>4 mm,多对称,尤见于内外侧隐窝。对照组滑膜难辨,RA组滑膜增厚、低回声、分界清、表面糙、见绒毛。彩超示RA组81.53%膝滑膜有明显血流信号,多为Ⅱ、Ⅲ级。RA组髌上囊液体厚度、滑膜厚度、Anti-ccp、ESR及CRP水平均高于对照组,滑膜动脉RI则低于对照组,差异有统计学意义(P<0.05);Anti-ccp、ESR及CRP阳性组髌上囊液体厚度、滑膜厚度水平均显著高于阴性组,滑膜动脉RI低于阴性组,差异有统计学意义(P<0.05)。髌上囊液体厚度、滑膜厚度与Anti-ccp、ESR及CRP水平均呈正相关(P<0.05);滑膜动脉RI与Anti-ccp、ESR及CRP水平均呈负相关(P<0.05)。结论高频超声可清晰观察RA患者的滑膜病变情况,且与Anti-ccp、ESR及CRP等实验室指标存在显著关联性,可为临床诊断RA滑膜病变患者提供有力的参考依据,利于制定更具针对性的治疗措施。

类风湿关节炎合并骨关节炎病人血清anti-Sa、anti-CCP水平与骨关节损伤、全身炎症反应的相关性分析

目的:分析类风湿关节炎(RA)病人血清anti-Sa、anti-CCP抗体水平与其骨关节损伤、全身炎症反应的相关性。方法:选择RA合并骨关节损伤病人108例,根据血清anti-Sa、anti-CCP抗体水平分别列入高anti-Sa组和低anti-Sa组、高anti-CCP组和低anti-CCP组。比较各组病人WOMAC骨性关节炎指数、lysholms膝关节功能评分值,血清白细胞介素(IL)-1β、IL-6、IL-27、肿瘤坏死因子α(TNF-α)水平。采用Pearson检验评估有关指标的相关性。结果:高anti-Sa组、高anti-CCP组病人的WOMAC骨性关节炎指数明显高于低anti-Sa组(P<0.01),lysholms膝关节功能评分明显低于低anti-Sa组(P<0.01);血清中IL-1β、IL-6、IL-27、TNF-α的水平明显高于低anti-CCP组(P<0.01)。RA病人血清anti-Sa、anti-CCP抗体水平与骨关节损伤、全身炎症反应严重程度呈正相关关系(P<0.05~P<0.01),与lysholms膝关节功能评分呈负相关关系(P<0.01)。结论:RA病人血清中anti-Sa、anti-CCP抗体水平显著升高与关节损伤及全身炎症反应有一定的相关性,可作为临床判断病情活动性与骨关节损伤的参考指标。

Experimental study of the anti-inflammatory activity of some compounds in Berchemia lineata(L.)DC

Objective:To screen the anti-inflammatory monomeric compounds isolated from Berchemia lineata(L.)DC and explore the anti-inflammatory mechanism of some compounds based on NF-κB signaling pathway.Methods:LPS was used to induce RAW264.7 to establish a model of cellular inflammatory reaction.CCK-8 method was used to detect the effect of monomer compounds on the activity of RAW264.7 cells.The release of nitric oxide(NO)in the superneant was measured by Griess method,and NO inhibition rate was calculated.The anti-inflammatory activity gradient of some monomeric compounds was also measured.The effects of monomer compound 21 on the secretion of IL-6,TNF-α,NF-κB,COX-2 and iNOS induced by LPS were detected by ELISA.Results:The concentration of monomer compound of Berchemia lineata(L.)DC.was 50μmol/L,and it was administered for 24 h.The results showed that anthraquinone compound No.19 had obvious drug toxicity,while other compounds had weak or no obvious drug toxicity.The concentration was 50μmol/L,and the drug was administered for 12 h.The results showed that all the monomer compounds could inhibit the release of NO to varying degrees,and the highest NO inhibition rate was over 90%,which showed obvious anti-inflammatory activity.NO inhibition rate of No.01 new skeleton compound can reach 70.81%.The results of anti-inflammatory activity gradient showed that the monomer compound of Berchemia lineata(L.)DC.could inhibit the release of NO in a dose-dependent manner.The results of ELISA showed that phenolic compound 21 could inhibit the secretion of IL-6,TNF-α,NF-κB,COX-2 and iNOS in RAW264.7 cells.Conclusion:The monomer compound of Berchemia lineata(L.)DC.has a certain anti-inflammatory activity,among which flavonoids and bibenzyl components isolated from this plant for the first time may be the material basis for its anti-inflammatory activity.The simple phenolic monomer compound 21 may play an anti-inflammatory role by regulating NF-κB signaling pathway.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone healing.Here,we used magnesium silicate nanospheres(MSNs)to load microRNA-146a-5p(miR-146a)to fabricate a nanobiomaterial,MSN+miR-146a,which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells(hDPSCs).In addition,miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages(BMMs)under lipopolysaccharide(LPS)stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6(TRAF6),and MSNs could simultaneously promote M2 polarization of BMMs.MiR-146a was also found to inhibit osteoclast formation.Finally,the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel.Collectively,the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oralmaxillofacial bone defects.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Multi-targeted anti-inflammatory drugs for the treatment of neurological disorders

Inflammation and kinase pathophysiology in neurological disorders:Inflammation is one of the common features of various acute and degenerative neurological disorders,such as stroke,traumatic brain injury(TBI),Alzheimer’s disease(AD),Parkinson’s disease(PD),and others.The inflammatory responses are manifested as the synthesis of inflammation mediators,recruitment of leukocytes,and other secondary injuries.Compelling evidence shows that a large number of inflammation mediators(e.g.,thrombin,reactive oxygen species,cytokines,chemokines,and other molecules)are implicated in the pathophysiological processes in neurological disorders(Liu and Ander,2012)(Figure 1).These increased inflammation mediators stimulate their downstream transmembrane receptors(e.g.,protease-activated receptors,cytokine receptors,and others),and further activate the intracellular downstream effector kinases,such as Src family kinase,Rho-associated protein kinase,Jun N-terminal kinase,extracellular signal-regulated kinase,cyclin-dependent kinase(CDK),and others(Liu and Ander,2012)(Figure 1).Aside from overlapping in different neurological disorders,numerous inflammatory molecules and multiple kinase-involved signaling pathways can be linked to a single neurological disorder such as AD(Heneka et al.,2015).Because of their pivot roles in the process of inflammation,kinases have been regarded as anti-inflammatory targets to improve outcomes of neurological disorders.

Bridging the gap:Unveiling the crisis of physical inactivity in inflammatory bowel diseases

In this editorial we comment on the article titled“Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity:The BE-FIT-IBD study”published in a recent issue of the World Journal of Gastroen-terology 2023;29(41):5668-5682.Inflammatory bowel diseases(IBD)are emerging as a significant global health concern as their incidence continues to rise on a global scale,with detrimental impacts on quality of life.While many advances have been made regarding the management of the disease,physical inactivity in these patients represents an underexplored issue that may hold the key for further and better understanding the ramifications of IBD.Chronic pain,fatigue,and fear of exacerbating symptoms promotes physical inactivity among IBD patients,while the lack of clear guidelines on safe exercise regimens contributes to a norm of physical inactivity.Physical activity(PA)is accepted to have a positive effect on disease outcomes and quality of life,while inactivity exacerbates comorbidities like cardiovascular disease and mental health disorders.The“BE-FIT-IBD”study,focusing on PA levels and barriers in IBD patients of Southern Italy,revealed that a significant proportion(42.9%)were physically inactive.This lack of PA is attributed to barriers such as fear of flare-ups and misconceptions about exercise exacerbating the disease.The study also highlighted the need for better communication between healthcare providers and patients regarding the benefits of PA and safe incorporation into lifestyles.Moreover,physical inactivity may also contribute to disability in IBD patients,having a great impact on employment status.Of note is the fact that IBD also comes with an important psychological burden with relevant evidence suggesting that regular PA can improve mood,reduce anxiety,and enhance mental health.The“BE-FIT-IBD”study advocated for the integration of PA into IBD management,emphasizing the bidirectional link between PA and IBD.Regular exercise can influence the course of IBD,potentially reducing symptom severity and prolonging remission periods.As such,it is mandatory that healthcare providers actively educate patients,dispel misconceptions,and tailor exercise recommendations to improve the quality of life and reduce IBD-related complications.

Interaction between inflammatory bowel disease,physical activity,and myokines:Assessment of serum irisin levels

Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of life.It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients.Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD patients.In addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis.Furthermore,irisin produces changes in the diversity of the microbiota.Therefore,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.