Marine soft corals as source of lead compounds for anti-inflammatories

Marine soft corals are known to produce a wide array of secondary metabolites,particularly diterpenoids and steroids,and often characterized by uncommon structural features and potent bioactivities.The remarkable abundance and diversity of bioactive small molecule which have been isolated from soft corals have made these organisms an important source of new drug candidates for human diseases,particularly for their anti-inflammatory activity.In this paper,the authors reported anti-inflammatory marine natural products isolated from diverse species of soft corals determined in vitro by their inhibition of lipopolysaccharide-induced expression of inducible NO synthase and cyclooxygenase-2 in murine macrophage cells(RAW 264.7).

Taurine: a promising nutraceutic in the prevention of retinal degeneration

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

A drug-loaded flexible substrate improves the performance of conformal cortical electrodes

Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.

Analgesic and anti-inflammatory activity of Cotinus coggygria Scop.extracts in vivo

Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to rats and mice(n=6)during hot plate,tail-flick,acetic acid-induced writhing,and formalin tests to determine its analgesic efficacy.The anti-inflammatory activity of C.coggygria extracts was evaluated by histamine and carrageenan-induced paw edema,cotton pellet-induced granuloma,and acetic acid-induced peritoneal capillary dye leakage tests.Results:C.coggygria extracts(50 and 100 mg/kg)significantly alleviated thermal and chemical-induced pain in rodents(P<0.05).It also demonstrated notable anti-inflammatory properties by mitigating histamine and carrageenan-induced paw edema,granuloma deposits,and vascular permeability(P<0.05).Moreover,C.coggygria extracts remarkably reduced TNF-α,IL-1β,IL-6,COX-2,and oxidative stress in rat paws(P<0.05).Carrageenan-induced histological aberrations in hind paw tissues were effectively(P<0.05)mitigated by treatment with C.coggygria extracts.Conclusions:C.coggygria Scop.extracts show analgesic and anti-inflammatory effects via inhibition of COX-2 and inflammatory and oxidative mediators.

Systematic review and network meta-analysis of different nonsteroidal anti-inflammatory drugs for juvenile idiopathic arthritis

BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.

New perspectives on the therapeutic potential of quercetin in non-communicable diseases:Targeting Nrf2 to counteract oxidative stress and inflammation

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applications of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Betalains protect various body organs through antioxidant and anti-inflammatory pathways

Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.

Micro-alloying of Zn and Ca in vacuum induction casted bioresorbable Mg system:Perspectives on corrosion resistance,cytocompatibility,and inflammatory response

There is an increasing interest in biodegradable materials,such as magnesium,for orthopaedic implants.This is driven by their potential to address challenges like stress shielding and the need for secondary removal surgery.In this study,biodegradable magnesium alloys were produced using the Vacuum Induction Casting technique.The impact of micro-alloying Zn and Ca in Mg-xZn-0.2Ca(x=0.1,0.2,0.3,and 0.4 wt%)alloys on corrosion resistance,cytocompatibility,and early-stage inflammatory response was investigated.XRD and SEM-EDS analysis confirmed the presence of Ca_(2)Mg_(6)Zn_(3)secondary phases in all alloys.The Mg-0.3Zn-0.2Ca alloy exhibited the lowest corrosion rate and an elastic modulus of 36.8 GPa,resembling that of natural bone.Electrochemical measurements indicated a correlation between grain size and secondary phase volume fraction in explaining corrosion behaviour.In vitro degradation in simulated body fluid(SBF)for 21 days showed hydroxyapatite formation on alloy surfaces,aligning with electrochemical studies.In vitro cytotoxicity tests demonstrated the cytocompatibility of all alloys,with Mg-0.3Zn-0.2Ca having the highest cell viability over a 6-day cell culture.Investigation into the inflammatory response with RAW-Blue macrophages revealed the anti-inflammatory properties of Mg-0.3Zn-0.2Ca alloys.Micro-alloying with 0.3 wt%Zn and 0.2 wt%Ca enhanced mechanical properties,corrosion resistance,cytocompatibility,and immunomodulatory properties.This positions the Mg-0.3Zn-0.2Ca alloy as a promising biodegradable implant for bone fixation applications.

Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies

Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Three anti-inflammatory polysaccharides from Lonicera japonica Thunb.:insights into the structure-function relationships

This study demonstrates the feasibility of producing three polysaccharides(neutral LJP-1,acidic LJP-2 and acidic LJP-3)with significant in vitro and in vivo anti-inflammatory activities from the flowers of Lonicera japonica.The three polysaccharides differed in chemical composition,molecular weight(Mw)distribution,glycosidic linkage pattern,functional groups and morphology.They exhibited excellent protective effects(in a dose-dependent manner)in lipopolysaccharide-injured RAW264.7 macrophages and Cu SO4-damaged zebrafish via reducing NO production and inhibiting the overexpressions of inflammation-related transcription factors,inflammatory proteins and cytokines in the NF-κB/MAPK signaling pathways.Their antiinflammatory effects varied owing to their different molecular characteristics and chemical compositions.Overall,LJP-2 at 400μg/m L was the most effective.LJP-2 consisted mainly of→5)-α-L-Araf(1→,→4)-α-LGalp A(1→and→2)-α-L-Rhap(1→residues with terminal T-β-D-Glcp.Thus,honeysuckle flowers are good sources of anti-inflammatory polysaccharides,and precise fractionation enables the production of potent antiinflammatory agents for the development of functional foods and healthcare products.

Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide

AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in rats.METHODS:RIRI was induced in Sprague Dawley rats through anterior chamber perfusion,and pretreatment involved administering LbGP via gavage for 7d.After 24h of reperfusion,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(CREA)levels,retinal structure,expression of Caspase-3 and Caspase-8,superoxide dismutase(SOD)activity,and malondialdehyde(MDA)in the retina were measured.RESULTS:The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer(GCL)and nerve fiber layer(NFL)of rats subjected to RIRI,as shown by light microscopy and optical coherence tomography(OCT).Serum AST was higher in the model group than in the blank group(P=0.042),but no difference was found in ALT,AST,and CREA across the LbGP groups and model group.Caspase-3 expression was higher in the model group than in the blank group(P=0.006),but no difference was found among LbGP groups and the model group.Caspase-8 expression was higher in the model group than in the blank group(P=0.000),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).SOD activity was lower in the model group than in the blank group(P=0.001),and the decrease was slower in the 400 mg/kg LbGP group than in the model group(P=0.003).MDA content was higher in the model group than in the blank group(P=0.001),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model.CONCLUSION:LbGP pretreatment exhibits dosedependent anti-inflammatory,and antioxidative effects by reducing Caspase-8 expression,preventing declines of SOD activity,and decreasing MDA content in the RIRI rat model.

Structural characterization and anti-inflammatory activities of novel polysaccharides obtained from Pleurotus eryngii

Natural polysaccharides named PEP-0.1-1,PEP-0-1 and PEP-0-2 from edible mushroom species Pleurotus eryngii were obtained in the present study.Results showed that molecular weights of these polysaccharides were 3235,2041 and 23933 Da,respectively.Further,structural characterization revealed that PEP-0.1-1 had a→4-α-D-Glcp-1→backbone and contained→4)-α-D-Glcp and→4)-β-D-Glcp reducing end groups.PEP-0-1 backbone contained→4-α-D-Glcp-1→and→6-α-3-O-Me-D-Galp-1→,and the side chains containedα-D-Glcp,β-D-Manp-1→andα-D-Glcp-3→.However,PEP-0-2 backbone consisted of→4-α-DGlcp-1→and→6-α-3-O-Me-D-Galp-(1→6)-α-D-Galp-1→while the side chains containedα-D-Glcp andβ-D-Manp-1→.Biological activity analysis was then carried out and found that all these polysaccharides could significantly suppress the relative mRNA expression of toll-like receptor 4,nitric oxide(NO),tumor necrosis factor-α,interleukin(IL)-1βand IL-6 in lipopolysaccharide(LPS)-induced inflammation of RAW264.7 cells,as well as the over secretion of the above cell cytokines.Moreover,Western blotting analysis revealed that all these purified fractions displayed significant inhibition effects on the expression of c-Jun N-terminal kinases protein induced by LPS in mitogen activated protein kinase pathway,along with the relieving on the inhibition effect of LPS on IκB-αprotein expression.In summary,the information generated by the present study could provide a theoretical basis for the exploration of novel healthy food materials from edible mushroom with antiinflammation activities.

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.

Prevalence and outcomes of neonates with severe COVID-19:An observational study at Children’s Hospital 1 in Ho Chi Minh City,Vietnam

Objective:To evaluate the impact of the severe COVID-19 pandemic on neonates and develop strategies to improve their outcomes.Methods:We conducted an observational cross-sectional study at Children's Hospital 1(CH1)from July 25,2021,to May 31,2022.All neonates who had fever or respiratory symptoms or were born from mothers with COVID-19 and had a positive RT-PCR SARS-CoV-2 result would be included.We classified neonates with COVID-19 into 2 groups:mild/moderate and severe for analysis.Differences between groups were analyzed using Fisher's exact test/Chi-square test for categorical variables and Student's t-test/Wilcoxon Rank Sum test for continuous variables.Results:This study included 88 newborns who had positive RT-PCR SARS-CoV-2 results.The severity COVID-19 rate among neonatal cases was found to be 13.6%(12/88),with a corresponding mortality rate of 1.1%(1/88).All severe cases showed lung abnormalities as evident on chest X-ray images.In addition to respiratory symptoms,a higher incidence of gastrointestinal manifestations,such as vomiting and diarrhea,was observed in the severe group,indicating a compelling association.The administration of anticoagulant and anti-inflammatory drugs in the study group resulted in a satisfactory outcome with no significant complications.Conclusions:The COVID-19 pandemic has had a substantial impact on the well-being of neonates.The management of COVID-19 in this population presents significant challenges.

Effect of simulated gastrointestinal digestion on antioxidant,and anti-inflammatory activities of bioactive peptides generated in sausages fermented with Staphylococcus simulans QB7

Dry-fermented sausages are a good source of bioactive peptides,whose stability against gastrointestinal(GI)digestion determines their bioaccessibility.This study focused on evaluating the effect of peptide extracts from sausages fermented with Staphylococcus simulans QB7 during in vitro simulated GI digestion,including peptide profiles and antioxidant and anti-inflammatory activities.Peptides present in sausages were degraded during digestion,with molecular weight reduced from>12 kDa to<1.5 kDa.Besides,the content of amino acids increased from 381.15 to 527.07 mg/g,especially tyrosine being found only after GI digestion.The anti-inflammatory activities were increased after GI digestion,however,the changes in antioxidant activities were the opposite.A total number of 255,252 and 386 peptide sequences were identified in undigested,peptic-digested and GI-digested samples,respectively.PeptideRanker,BIOPEP-UWM and admetSAR were used to further predict the functional properties and intestinal absorption of the identified peptide sequences from GI digestion.Finally,18 peptides were discovered to possess either antioxidant or anti-inflammatory capacities.

Hydration transformation behaviors of CO_(2) and excellent anti-inflammatory activity on RAW 264.7 cell

Skin care products with carbonic acid(H_(2)CO_(3))have gained extensive attention worldwide.However,the conversion of CO_(2) to H_(2)CO_(3) is not stable,and the mechanism of the effect of H_(2)CO_(3) on skin care has not been clearly proved.The hydration-dissolution behaviors of CO_(2) were investigated under different temperature,pH,and pressure conditions.Moreover,based on the phenomenon of CO_(2) hydration transformation,the inflammatory effect of CO_(2) hydrate on macrophages(RAW 264.7)was investigated.The result shows that the increase in temperature weakened the hydration of CO_(2),and the increase in pH and pressure both promoted the water-phase transformation of CO_(2).When pH<6,CO_(2) reacts with water to generate H_(2)CO_(3).When pH was between 6-7,the prompt solution was a mixture of H_(2)CO_(3) and HCO_(3)^(-).When the pH was between 7-9,they mainly generated HCO_(3)^(-).And when pH>9,CO_(2) solubility mainly converts to CO_(3)^(2-).Besides,CO_(2) can inhibit the secretion of inflammatory factors by RAW 264.7 cells by inhibiting the phosphorylation of the p38 protein.CO_(2) hydrate inhibited the expression of pro-inflammatory factors IL-6,TNF-α,and up-regulated the expression of anti-inflammatory factor IL-10.Furthermore,the anti-inflammatory molecular mechanism of CO_(2) hydration inhibited the MAPK signaling pathway by inhibiting the phosphorylation of p38.The hydration-dissolution behavior of CO_(2) was investigated.This work revealed the anti-inflammatory bioeffect of CO_(2) hydrate,providing a theoretical basis and application support for CO_(2) skin care products.

Trends in upper gastrointestinal bleeding management

Upper gastrointestinal bleeding(UGIB)can be attributed to either non-variceal or variceal causes.The latter is more aggressive with hemodynamic instability secondary to decompensated cirrhosis and portal hypertension.Non-variceal UGIB(NVUGIB)occurs due to impaired gastroprotective mechanisms attributed to several drugs such as anticoagulants and nonsteroidal anti-inflammatory drugs.Helicobacter pylori infection contributes to the development of peptic ulcer bleeding as well.NVUGIB presentation can be either hemodynamically stable or unstable.During the initial assessment a scoring system including patient-related factors(current cardiac,renal,and liver diseases and hemodynamic and labo-ratory parameters)is used to determine the patient’s prognosis.The Glasgow Blatchford score has been shown to be the most useful and precise.Those with high-risk NVUGIB require urgent assessment and upper endoscopy to achieve better short-term and long-term outcomes such as less hospitalization,blood transfusion,and surgery.

Timing impact on the initiation of pirfenidone therapy on idiopathic pulmonary fibrosis disease progression

In this editorial,we comment on the article by Lei et al,with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone(PFD)in the management of idiopathic pulmonary fibrosis(IPF)and its impact on lung function of IPF patients.PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages.It inhibits various pathways and has antifibrotic,anti-inflammatory,and antioxidant properties.Despite dosage lowering,PFD slowed IPF progression and maintained functional capacity.The 6-min walk distance test indicated that patients tolerated adverse events well,and PFD significantly reduced the incidence of progression episodes and death.Even when a single disease-progression event occurred,continuing PFD treatment had benefits.