Acid Suppression Research Articles

Roles of traditional Chinese medicine extracts in hyperuricemia and gout treatment: Mechanisms and clinical applications

In this manuscript, we comment on the article by Liu et al published in the recent issue of the journal. Hyperuricemia (HUA) has become the second most common metabolic disease after type 2 diabetes mellitus and is the most important risk factor for gout. This discussion focuses on the targets and clinical application value of traditional Chinese medicine (TCM) extracts in the treatment of HUA and gout, emphasizing the role of gut microbiota. Liu et al ’s study demonstrated that Poecilobdella manillensis protein extract alleviated HUA through multiple mechanisms, including inhibition of uric acid (UA) reabsorption, promotion of UA excretion, repair of intestinal barrier function, and regulation of gut microbiota and metabolome. Unlike the commonly used urate-lowering drugs such as allopurinol and febuxostat, which have clear and single targets, many TCMs have multi-target effects. However, the active components and mechanisms of TCMs are not fully understood, limiting their clinical application in the treatment of HUA and gout. Additionally, the role of gut microbiota in UA metabolic homeostasis needs to be further explored.

A Simple Prediction Model for Clostridioides difficile Infection: A Hospital-Based Administrative Database Study.

Few prediction scores for Clostridioides difficile infection (CDI), a potentially life-threatening nosocomial diarrhea, combine high accuracy with simplicity. A simple prediction score for routine clinical practice is needed. We conducted a retrospective cohort study of all inpatients aged ≥ 18 at a secondary care hospital in Japan. The derivation and validation cohorts consisted of patients from January 2016 to December 2020 and January 2021 to September 2022, respectively. Demographic and clinical data were retrieved using electronic medical records and an administrative database. The primary outcome was to derive and validate an accurate, simple prediction score for primary hospital-onset CDI. A derived prediction score by logistic regression analysis was calibrated and validated. CDI developed in 102 of 25 517 and 25 of 6259 patients in the derived and validation cohorts (2.7 cases/10 000 patient-days). The derived model for predicting CDI, including antibiotic use, acid suppressant (proton pump inhibitors or vonoprazan) use, Charlson comorbidity index, and Barthel index, yielded c-statistics of 0.89 and 0.82 in the derivation and validation cohort. The model was well calibrated. This simple prediction score enables early medical intervention and modification of treatment plans to reduce the risk of developing primary hospital-onset CDI.

A Comprehensive Review on Novel Potassium Competitive Acid Blocker Vonoprazan in the Treatment of Gastrointestinal Disorders

Vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), represents a significant advancement in the management of acid-related disorders. This novel agent demonstrates rapid, potent, and sustained acid suppression through its unique mechanism of reversibly binding to the gastric H+/K+-ATPase proton pump. Vonoprazan maintains stable inhibition of acid secretion regardless of CYP2C19 polymorphisms, offering advantages over traditional proton pump inhibitors (PPIs). Clinical studies have established its superior efficacy in treating various acid-related conditions, including gastroesophageal reflux disease (GERD), peptic ulcer disease, and Helicobacter pylori infection. The drug exhibits remarkable healing rates in erosive esophagitis and maintains long-term remission effectively. In H. pylori eradication therapy, vonoprazan-based regimens have shown higher success rates compared to conventional PPI-based treatments, particularly in areas with high antibiotic resistance. The pharmacokinetic profile of vonoprazan allows for flexible dosing schedules and rapid onset of action, enhancing patient compliance. Safety analyses from long-term studies indicate a favorable tolerability profile, with most adverse events being mild to moderate in severity. The emergence of vonoprazan has expanded therapeutic options for acid-related disorders, particularly benefiting patients who show inadequate response to conventional PPI therapy. Recent data also suggest potential applications in prevention of low-dose aspirin-induced ulcers and management of non-erosive reflux disease (NERD).

Tranexamic Acid With Acid Suppression Versus Acid Suppression Alone as Therapy for Upper Gastrointestinal Bleeding: A Meta-Analysis of Randomized Controlled Trials.

Studies have reported the benefits of tranexamic acid (TXA) in controlling bleeding across various conditions. However, the effect of TXA in upper gastrointestinal bleeding (UGIB) remains controversial, and its therapeutic impact when combined with acid suppression, particularly proton pump inhibitors (PPIs), which are considered first-line therapy for bleeding peptic ulcers, has not been reported. We systematically searched PubMed, Embase, and Google Scholar from January 1987 to June 2024 using predefined keywords to identify RCTs meeting our inclusion criteria, including details of TXA dosage, route of administration, and choice of acid suppressants. Data from selected trials were extracted, and a meta-analysis was performed using random-effects modeling. Six trials with 709 participants were included. Baseline patient characteristics in the selected trials were balanced. The rebleeding rate, mortality, need for blood transfusion, units of blood transfused, and need for salvage therapy were compared. The TXA with acid suppression group significantly reduced the risk of rebleeding (RR: 0.63, 95% CI: 0.41-0.96), units of blood transfused (mean difference: -1.08, 95% CI: -1.44 to -0.71), and the need for salvage therapy (RR: 0.28, 95% CI: 0.12-0.64). No significant difference was observed in mortality rate (RR: 0.74) and need for blood transfusion (RR: 1.01) between the two groups, but outcomes favored the TXA and acid suppression group. We suggest combining TXA with acid suppression as a first-line therapy for UGIB patients. Further trials should be conducted to determine the optimal dose and route of TXA administration for better care.

Proteomic analysis of mouse liver lesions at all three stages of Echinococcus granulosus infection.

Echinococcus granulosus, a zoonotic parasite, can severely damage host health or even lead to host death. In humans, early diagnosis of E. granulosus infection is difficult because the initial stages of the infection tend to be asymptomatic, this delays treatment and worsens prognosis in most patients. Herein, we present a comprehensive, temporal proteomic atlas of the liver at three stages of E. granulosus infection and analyze the changes in the proteome of host focal lesions; this atlas may provide an overview of the effects of E. granulosus in the host, as well as the interactions between them. We identified 3,197 proteins from mice model at 1, 3, and 6 months after E. granulosus infection; of these proteins, 760 were differentially expressed (520 upregulated; 240 downregulated). Moreover, 228 differentially expressed proteins were screened through cluster analysis and classified into four clusters according to their changing trends. Subsequently, candidate molecules related to cyst invasion, growth, candidate pathways and proteins related to angiogenesis were noted to demonstrate important value in mouse liver. Next, we used western blotting to verify the presence of the aforementioned proteins in mouse liver. In the later stages, E. granulosus infection was noted to result in significant enrichment of crucial proteins facilitating protoscoleces growth and development and inhibition of amino acid and lipid metabolic enzyme expression in mouse liver; it was also noted to transform host metabolism by weakening oxidative phosphorylation and enhancing glycolysis. In conclusion, we explored the molecular mechanisms underlying the parasitic processes of E. granulosus through proteomic analysis. Our results provide evidence that may enable the exploration of core regulatory targets for early and effective diagnosis and immunotherapy of E. granulosus infection, as well as parasite-host interactions involved in cystic echinococcosis development.

Lactobacillus fermented chickpeas: Improving dough process quality and biscuit nutritional value

This study aimed to examine the impact of lactobacillus fermented chickpeas (LFC) on dough quality and assess their application potential in biscuits. The results of rheological properties showed that LFC significantly increased the storage modulus (G') and loss modulus (G'') of the dough, with a greater increase in G'. The textural analysis showed that the LFC significantly increased the hardness of the dough before and after fermentation. In the low-field NMR analysis, LFC enhanced the bound water content of the dough and reduced the mobility of the water molecules. Furthermore, the network structure of gluten proteins was weakened by LFC, resulting in more exposed starch. In vitro protein digestibility increased by 28.01% at the gastric end and 11.76% at the intestinal end of LFC-biscuits as compared to chickpea biscuits. It was associated with lactobacilli fermentation reducing phytic acid and trypsin inhibitor activity in chickpeas. Moreover, the protein content of the biscuits has been increased (33.26%) and their free amino acid composition has been optimized. The hardness, brittleness, and specific volume of biscuits were significantly enhanced by LFC, with well sensory acceptance. These findings will enrich the theory of lactobacilli fermentation of legumes and inspire its application in baked foods.

PPARγ and COX1 Inhibition of Linoleic Acid as Potential Bioactive Molecule in Aqueous Extract of Tinospora cordifolia (Wild.): A in silico based Approach

In this work, the ethyl acetate extract of Tinospora cardifolia was analyzed using GC-MS and phytochemical analysis. The FTIR analysis and UV spectroscopy were used to further validate the structures of the isolated compounds. For the selected compounds, the computational methods were used to conduct an in silico analysis on their molecular, physico-chemical and druglikeliness properties. Moreover, the pharmacokinetic profile and additional toxicity potential were ascertained. Swiss ADME tools and OSIRIS data warrior were used in the investigation. The docking experiment was used to examine the anti-inflammatory and antidiabetic characteristics. The α-glucosidase, peroxisome proliferator-activated receptor, glucose transporter-1 and cyclooxygenases 1 and 2 were targeted for inhibition. Approximately 23 chemicals were found during GC-MS analysis. Each of the compounds have shown the pharmacokinetic potential and moderate to good drug likeliness. The compounds bioactivity score against enzyme receptors was high. The least harmful profile of PGP and CYP inhibitory actions was indicated by the ADMET prediction. Linoleic acid (molecule-12) has a strong binding affinity for PPARγ and COX1 targeted proteins under inquiry as demonstrated by the docking studies.

Optimizing epidermal growth factor receptor-tyrosine kinase inhibitor treatment in lung cancer: a systematic review and meta-analysis of the influence of gastric acid suppressants.

The introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has revolutionized advanced non-small cell lung cancer (NSCLC) treatment. However, their efficacy can be compromised by concurrent use of gastric acid suppressants (GASs), such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs). This study aimed to update the evidence on the impact of GASs on the overall survival (OS) and progression-free survival (PFS) in patients on EGFR-TKI treatment. A systematic review and meta-analysis were conducted using data from PubMed, Embase, Cochrane Library, Web of Science, Scopus, KoreaMed, and preprint repositories. Data from 13 retrospective studies, involving 10,814 patients, were analyzed. Overall, 34.6% of the patients used GASs, with most being Asian females and non-smokers. Most patients had EGFR-mutated adenocarcinoma, reflecting typical EGFR-TKI usage scenarios. Concurrent use of GASs was significantly associated with reduced OS [hazard ratio (HR) =1.34, 95% confidence interval (CI): 1.26-1.42], and PFS (HR =1.52, 95% CI: 1.25-1.86). In subgroup analysis, PPIs had a more negative impact on OS (HR =1.64, 95% CI: 1.51-1.79) than did H2RAs (HR =1.11, 95% CI: 0.95-1.31). Longer overlap times of GASs correlated with a higher trend in HRs for OS. However, the results for PFS were not significant in both subgroup analyses. Concurrent use of GASs with EGFR-TKIs is linked to poorer OS and PFS in patients with advanced NSCLC. Careful consideration is advised when prescribing GASs, including adjusting administration timing, minimizing overlap duration, or opting for H2RAs over PPIs. Further research is needed to optimize treatment protocols, specifically addressing the duration of overlap time, to improve patient outcomes.

Retinoic acid inhibition of cell proliferation via activation of CDKN1B signaling in the forebrain and spinal cord during mouse embryonic development

BackgroundThe active metabolite of vitamin A (retinol) is retinoic acid (RA). RA is essential for developing several organs as a signaling molecule that is tightly regulated during embryogenesis. We explored the teratogenic effects of RA on forebrain and spinal cord development modified by cyclin-dependent kinase inhibitor 1B (CDKN1B), as the mechanism underlying RA's teratogenic impacts requires further investigation. The study involved four groups of pregnant mice: the negative control group, the positive control group treated with dimethyl sulfoxide (DMSO) diluted in sunflower oil, the RA-treated group receiving a low dosage (5 mg/kg), and the RA-treated group receiving a high dosage (10 mg/kg). The treatment groups received daily intraperitoneal RA dissolved in DMSO and diluted with sunflower oil on gestational days 10.5, 11.5, and 12.5. On day 13.5 of pregnancy, the pregnant mice were euthanized by cervical dislocation, and immunohistochemical analyses of brain and spinal cord tissues were performed.ResultsMorphologically, we observed a decrease in the number of implantation sites and the presence of hematomas in several uterus areas in the high-dose RA (10 mg/kg) group. Additionally, RA was shown to cause adverse changes in uterine weight and length. RA treatment indicated elevated levels of CDKN1B expression in spinal cord development, the diencephalon, and the telencephalon.ConclusionOur findings demonstrated that by activating CDKN1B as an RA target gene for cell cycle arrest, an excess of RA during brain development in mouse embryos can induce cell undifferentiation during development.

Alternative Uses of Fermented Wheat Bran: A Mini Review

Bran is a by-product primarily derived from the milling of grains, notably wheat and rice. It is rich in dietary fiber, vitamins, minerals, and phytochemicals yet often remains underutilized in its raw form. This raw material is abundant and readily available, offering significant potential for value-added applications. In its unprocessed state, bran boasts a complex chemical composition that includes proteins, lipids, and carbohydrates. However, it also contains antinutritional components such as phytic acid and enzyme inhibitors, which may limit its nutritional efficacy. Through further processing or storage, these components can be transformed to enhance their antioxidant properties and overall nutritional value. Bran is used in both animal feed and human food applications, though its use is often hindered by its high fiber content and antinutritional factors. To maximize its utility, innovative processing techniques are required to improve its digestibility and nutrient availability. Fermentation presents a viable method for enhancing the nutritional profile of bran. This process typically employs microorganisms such as bacteria, yeast, or fungi to break down complex compounds, thereby increasing the bioavailability of nutrients. After fermentation, bran exhibits improved chemical composition and nutritional value. The process reduces antinutritional components while enriching the bran with beneficial compounds like amino acids and probiotics. Utilizing fermented bran in animal feed offers numerous advantages, including enhanced digestive health, improved nutrient absorption, and augmented disease resistance. It serves as a sustainable feed alternative that supports livestock growth while aligning with ecological goals. The processing of bran through fermentation not only maximizes its nutritional potential but also contributes to sustainable agricultural practices by reducing waste. Future research should focus on optimizing fermentation techniques and exploring novel applications in both feed and food industries to fully realize the benefits of this versatile by-product.

Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy.

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function and contributes to immunotherapy failure. However, acidic conditions in the TME disrupt the interaction between cancer and immune cells, driving tumor-infiltrating T cells and NK cells into an inactivated, anergic state. Simultaneously, acidosis promotes the recruitment and activation of immunosuppressive cells, such as myeloid-derived suppressor cells and regulatory T cells (Tregs). Notably, tumor acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor acidity thus acts as a "protective shield," neutralizing anti-tumor immune responses and transforming immune cells into pro-tumor allies. Therefore, targeting lactate metabolism has emerged as a promising strategy to overcome this barrier, with approaches including buffer agents to neutralize acidic pH and inhibitors to block lactate production or transport, thereby restoring immune cell efficacy in the TME. Recent discoveries have identified genes involved in extracellular pH (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims to elucidate the molecular mechanisms driving extracellular acidification and to develop treatments that modulate pH levels to enhance immunotherapy outcomes. Additionally, future clinical studies are crucial to validate the safety and efficacy of pHe-targeted therapies in cancer patients. Thus, this review explores the regulation of pHe in the TME and its potential role in improving cancer immunotherapy.

Retrospective Analysis of Pregnant Cases in Terms of Drug-Drug interactions and Teratogenic risks

Objective: While teratogenic risks in pregnant women are frequently discussed, polypharmacy and drug-drug interactions (DDI) are topics with little known information. The aim of this study is to determine the polypharmacy status, DDI, and teratogenic risk profile during pregnancy. Method: A retrospective cohort study was conducted covering the year 2023 on pregnant women who were referred for pharmacology consultation due to a history of drug use. Investigation of DDI was performed through the Micromedex and Medscape online query modules. Results: It was found that 113 pregnant women used a total of 71 different active ingredient drugs from 24 diverse pharmacological groups. The average number of drugs used per individual was 2.97. Analgesics, antibiotics, and gastric acid inhibitors were the most used medications, respectively. 11.6% of the women had a comorbidity, and cardiovascular diseases were the most common. It was determined that 28.3% of women had a serious or moderate DDI. The rate of drugs in categories D and X, which are particularly risky in terms of teratogenicity, was found to be 40.8%. Conclusion: In addition to teratogenic effects, polypharmacy and DDI are also significant risk factors in pregnant women. There is still a crucial need for evidence on the medications prescribed in pregnancy, how it specifically affects women with comorbidities, and related benefits and harms.

MGB-OAGB International Club-Results of a Modified Delphi Consensus on Controversies in OAGB.

One anastomosis gastric bypass (OAGB) presently constitutes 7.6% of all metabolic and bariatric surgery (MBS) procedures globally. Despite being approved by the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) as a standalone MBS procedure and two consensus efforts in the past, multiple areas of controversies remain. This consensus builds upon previous consensus efforts to address unresolved controversies in the field. A modified Delphi consensus exercise was conducted over 4weeks under the aegis of the MGB-OAGB International Club. A panel of 86 bariatric experts from 25 countries participated in 3 rounds of voting on 29 questions on patient selection, technical standardization, revisional surgeries, and post-operative care. Consensus was defined as at least 70% agreement. Consensus was achieved on 22 out of 29 questions. Key areas of agreement included suitability of OAGB for adolescents above the age of 15years and patients with class 1 obesity with uncontrolled type 2 diabetes. Patients with severe esophagitis and Barrett's esophagus were not considered as good candidates for OAGB. Crural repair with OAGB was considered as an appropriate procedure in patients with large hiatus hernia. While a bilio-pancreatic limb (BPL) length of 150 - 200cm was deemed suitable, it was recommended to tailor the BPL length to prevent protein energy malnutrition. It was also agreed to routinely administer ursodeoxycholic acid and proton-pump inhibitors for 6months post-operatively. This modified Delphi consensus represents a critical step forward in addressing the controversies surrounding OAGB. It also emphasizes on the importance of individualized patient care and the need for ongoing research to refine surgical practices and improve outcomes.

Antinutritional factors and protein digestibility of broad bean flours hydrolysed during soaking using vacuum enzyme impregnation

The hydrolysis of legume proteins improves their nutritional and functional properties. Usually done by mixing flour with an enzyme solution, the process can be simplified using vacuum enzyme impregnation during soaking. This study used vacuum impregnation with papain or bromelain to obtain hydrolysed broad bean flours. It examined the impact of vacuum impregnation and enzyme incorporation on hydration kinetics and the impact of hydrolysis and dehulling on antinutritional factors and protein digestibility. Vacuum impregnation accelerated hydration and enzyme incorporation did not alter the hydration rate. Maximum hydrolysis degrees were 9.1 % with papain and 8.8 % with bromelain after 4 h of soaking. Hydrolysis increased phytic acid, total phenolics, and tannins content while decreasing trypsin inhibitors. Dehulling increased phytic acid and trypsin inhibitors, reduced tannins, and enhanced protein digestibility. Vacuum enzyme impregnation during soaking was effective for hydration and protein hydrolysis, modifying the nutritional properties of broad bean flours.

Effects of Tegoprazan, Potassium-Competitive Acid Blocker, on the Gastric Emptying and Postprandial Symptoms in Healthy Humans.

Proton pump inhibitors are potent gastric acid inhibitors. However, they may worsen symptoms such as postprandial fullness and early satiation by reducing gastric emptying (GE). This study aims to evaluate the effects of tegoprazan, a new potassium-competitive acid blocker, on GE and dyspeptic symptoms. A randomized, double-blind, placebo-controlled design was adopted for this study. Participants underwent GE tests and responded to a questionnaire regarding gastrointestinal symptoms before and after administration of tegoprazan 50mg. GE was assessed using scintigraphy over 4h with a standardized solid meal. Thirty participants were recruited (19 men, mean age 28.2 ± 7.3years). After medication, no significant differences were observed in gastric half emptying time (T1/2) and gastric retention at 4h (GE 4h) between the tegoprazan and the control group (114.2 ± 48.9min vs. 93.7 ± 34.7min, P = 0.20; 10.1 ± 12.0% vs. 4.3 ± 5.4%, P = 0.11, respectively). Furthermore, there were no statistically significant differences detected in the changes within each group between two groups (T1/2, 9.9 ± 52.7min vs. -4.7 ± 30.5min, P = 0.36; GE 4h, 5.2 ± 13.9% vs. -1.3 ± 6.5%, P = 0.12). The changes in dyspeptic symptom scores after tegoprazan administration did not significantly differ from those in the control group with no correlation between symptoms and GE parameters. In healthy adults, the administration of tegoprazan did not show a significant impact on GE and dyspeptic symptoms, especially postprandial fullness or early satiation.

Deciphering the function of Fe3O4 in alleviating propionate inhibition during high-solids anaerobic digestion: Insights of physiological response and energy conservation

Fe3O4 is a recognized addictive to enhance low solid anaerobic digestion (AD), while for high solid AD challenged by acidity inhibition, its feasibility and mechanism remain unclear. In this study, the positive effect of Fe3O4 on high-solids AD of food waste by regulating microbial physiology and energy conservation to enhance mutualistic propionate methanation was documented. The methane yield was increased by 36.7 % with Fe3O4, which because Fe3O4 alleviated propionate stress on methane generation, along with improved propionate degradation and methanogenic metabolism. Fe3O4 facilitated the production of extracellular polymeric substances and the formation of tightly bio-aggregates, fostering an enriched microbial population (e.g., Smithella and Methanosaeta) to resist propionate stress. Also, Fe3O4 up-regulated the genes in stress defense system, cytomembrane biosynthesis/function, metal irons transporter, cell division and enzyme synthesis, verifying its superiority on cellular physiology. In addition, energy-conservation strategies related to intracellular and extracellular electron transfer were enhanced by Fe3O4. Specifically, the enzyme expressions involved in reversed electron transfer and electron bifurcation coupled with direct interspecies electron transfer (DIET) were upregulated by at least 2.2 times with Fe3O4, providing sufficient energy to drive thermodynamic adverse methanogenesis from propionate-stressed condition. Consequently, the reinforced enzyme expression in the dismutation and DIET pathway make it to be the predominant drivers for enhanced methanogenic propionate metabolism. This study fills the knowledge gaps of Fe3O4-induced microbial physiological and energetic strategies to resist environmental stress, and has remarkable practical implicated for restoring inhibited bioactivities.

Expert opinion on the prescription practice of a combination of rabeprazole and domperidone for managing nighttime heartburn in GERD among Indian patients

The synergistic effect of Rabeprazole and Domperidone suggested a more comprehensive treatment strategy, targeting both acid suppression and motility enhancement in GERD management in several clinical studies. However, studies regarding their prescription practices of this combination is scarce. This study aimed to gather comprehensive insights into various aspects of gastroesophageal reflux disease (GERD) management in Indian settings.This cross-sectional study was conducted from June 2023 to December 2023 using a 24-item structured questionnaire distributed via email and online platforms. Clinicians completed the survey independently, with the option to skip questions and provided written informed consent. The questionnaire covered GERD management aspects, including patient demographics, clinical challenges, treatment preferences, efficacy of treatment combinations, patient adherence, use of guidelines, comorbidities, risk factors and patient education methods.According to 39% of clinicians, 31-40 GERD patients per month report nighttime heart burn, while another 39% reported it as 21-30 cases monthly. Majority of the clinicians (95.65%) preferred rabeprazole for its longer action in managing nighttime heartburn in GERD. According to 96% and 89% of the clinicians, respectively, the combination of rabeprazole and domperidone was favored for managing nighttime heartburn and was more effective than other PPI combinations. Nearly 93% stated that this combination provides the fastest relief. The recommendation for taking the combination once a day was made by 67% of clinicians and 59% reported that their patients felt relieved within 1-2 weeks. Helirab D was preferred due to its advanced release profile 2 (ARP2) technology by 50% of clinicians.There was a strong clinical preference for using a combination of rabeprazole and domperidone to manage nighttime heartburn in patients with GERD. This combination seems to have advantages in terms of effectiveness, quick onset of action and relief for patients. The once-daily dosing schedule and formulation technology (ARP2) may be contributing factors to its popularity among clinicians.

A Comprehensive Review on the Antibacterial, Antifungal, Antiviral, and Antiparasitic Potential of Silybin.

Silybin, a flavonolignan extracted from the seeds of the plant species Silybum marianum (L.) Gaertn., has a variety of pharmacological activities, including antimicrobial activity against several microorganisms of clinical interest. This review analyzes the existing studies on silybin's antimicrobial activity and possible mechanisms of action. Silybin has been shown to inhibit the growth of Gram-positive and Gram-negative bacteria, as well as some fungi, viruses, and protozoa. In general, possible mechanisms of antimicrobial action include the inhibition of efflux pumps, prevention of biofilm formation, reduction of the expression of virulence factors, induction of apoptosis-like effects, and plasma membrane damage, as well as the inhibition of nucleic acid and protein synthesis. Silybin has been shown to have synergistic effects when combined with conventional antibiotics against both drug-sensitive and drug-resistant microorganisms. However, the low bioavailability observed for this flavonolignan has been a challenge to its clinical use. In this context, nanotechnology has been used to increase silybin's bioavailability while enhancing its antimicrobial activity. Furthermore, certain structural modifications have been able to enhance its antimicrobial activity in comparison to that of the natural molecule. Overall, this review provides insights into the scientific understanding of the mechanism of action of silybin and its desired properties for the effective treatment of infections.

Effects of Medication Period and Gastrin Levels on Endoscopic Gastric Mucosal Changes in Long-Term Proton Pump Inhibitor Users.

Background/Objectives: Proton pump inhibitor (PPI) use has increased worldwide, including in continuous and longer-term users. Recent reports highlight PPI-related endoscopic gastric mucosal changes, including fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cracked and cobblestone-like mucosa (CCLM), and black spots. PPI use elevates gastrin levels because of acid inhibition, and hypergastrinemia might be relevant to these findings. In this cross-sectional study, we retrospectively examined gastric mucosal changes in long-term PPI users, focusing on medication period and gastrin levels. Methods: We enrolled 57 patients who received a PPI (>1 year) at two clinics between January 2021 and March 2022. Participants were classified according to medication period: 1 < 5, 5-10, and ≥10 years. Gastrin levels were categorized as low, middle, and high (<250, 250-500, and ≥500 pg/mL, respectively). Odds ratios (OR) were estimated to assess the risk of endoscopic findings. Results: Of the 57 patients, 6 (10.5%), 25 (43.9%), and 26 (45.6%) were PPI users of 1 < 5, 5-10, and ≥10 years, respectively. There were no significant differences in the incidence of endoscopic findings among the medication periods. Low, middle, and high gastrin groups included 21 (36.8%), 21 (36.8%), and 15 (26.3%) patients, respectively. CCLM incidence was significantly elevated in higher gastrin level groups: middle (OR, 6.60; 95% confidence interval [CI], 1.46-29.75; p = 0.014) and high (OR, 9.00; 95% CI, 1.79-45.23; p = 0.0008) (p-trend = 0.0171). No significant differences were observed for other findings. Conclusions: No elevated risk of PPI-related gastric epithelial changes in long-term PPI users was observed time-dependently. Notably, higher gastrin levels were positively associated with CCLM development, irrespective of the medication period.

Functional food candidate from Indonesian green algae Caulerpa racemosa (Försskal) J. Agardh by two extraction methods: Metabolite profile, antioxidant activity, and cytotoxic properties

There is an urgent need to explore natural sources like Caulerpa racemosa (Försskal) J. Agardh for bioactive compounds with strong antioxidant and therapeutic potential, providing sustainable alternatives for health and pharmaceutical innovation. This study aimed to determine the phytochemical profile and biological activities of extracts from edible green algae–known as sea grapes (C. racemosa). This present study has successfully identified secondary metabolites through untargeted metabolomic profiling by liquid chromatography-high resolution mass spectrometry (LC-HRMS) as well as a bioactive peptide. The antioxidant activity and cytotoxicity of extracts from C. racemosa and compounds were determined. A total of 103 metabolites were identified in the C. racemosa extract obtained by the maceration (ME), while 48 metabolites were detected in the soxhlet extract (SE). The sequence of the identified peptide was ELWKTF (Glu-Leu-Trp-Lys-Thr-Phe; C41H58N8O) and its abundance was identified in the α-chymotrypsin hydrolysate of C. racemosa. In the antioxidant activity test, SE and purified fraction 1 (PF1) had EC50<EC50 of control or Glutathione (GSH) in terms of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) inhibition, and PF1 had EC50<EC50 of control or Trolox in terms of 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) inhibition. In general, C. racemosa contains antioxidant nutrients, metabolites, and bioactive peptides, suggesting its promising potential as a functional food and pharmaceutical.