Sjögren's syndrome is a chronic inflammatory autoimmune disease characterized by diminished secretory function of the exocrine glands. Although extensive investigation has been done to understand Sjögren's syndrome, the causes of the disease are as yet unknown and treatments remain largely ineffective, with established therapeutic interventions being limited to use of saliva substitutes with modest effectiveness. A primary feature of Sjögren's syndrome is uncontrolled inflammation of exocrine tissues and previous studies have demonstrated that lipid-based specialized pro-resolving mediators reduce inflammation and restores tissue integrity in salivary glands. However, these studies are limited to a single specialized pro-resolving lipid mediator's family member resolvin D1 or RvD1 and its aspirin-triggered epimer, AT-RvD1. Consequently, additional studies are needed to explore the potential benefits of other members of the specialized pro-resolving lipid mediator's family and related molecules (e.g., additional resolvin subtypes as well as lipoxins, maresins and protectins). In support of this goal, the current review aims to briefly describe the range of current experimental methods to investigate the impact of specialized pro-resolving lipid mediators on Sjögren's syndrome, including both strengths and weaknesses of each approach where this information is known. With this article, the possibilities presented by specialized pro-resolving lipid mediators will be introduced to a wider audience in immunology and practical advice is given to researchers who may wish to take up this work.

MEK inhibitors are among the most successful molecularly targeted agents used as cancer therapeutics. However, to treat cancer more efficiently, resistance to MEK inhibitor-induced cell death must be overcome. Although previous genetic approaches based on comprehensive gene expression analysis or RNAi libraries led to the discovery of factors involved in intrinsic resistance to MEK inhibitors, a feasible combined treatment with the MEK inhibitor has not yet been developed. Here, we show that a chemoproteoinformatics approach identifies ligands overcoming the resistance to cell death induced by MEK inhibition as well as the target molecule conferring this resistance. First, we used natural products, perillyl alcohol and sesaminol, which induced cell death in combination with the MEK inhibitor trametinib, as chemical probes, and identified ribosomal protein S5 (RPS5) as their common target protein. Consistently, trametinib induced cell death in RPS5-depleted cancer cells via upregulation of the apoptotic proteins BIM and PUMA. Using molecular docking and molecular dynamics (MD) simulations, we then screened FDA- and EMA-approved drugs for RPS5-binding ligands and found that acetylsalicylic acid (ASA, also known as aspirin) directly bound to RPS5, resulting in upregulation of BIM and PUMA and induction of cell death in combination with trametinib. Our chemoproteoinformatics approach demonstrates that RPS5 confers resistance to MEK inhibitor-induced cell death, and that aspirin could be repurposed to sensitize cells to MEK inhibition by binding to RPS5.

The fungi causing fruit rot were isolated from symptomatic Shengzhou nane (Prunus salicina var. taoxingli) fruit and were identified as Aspergillus niger by biological characteristics and molecular analysis of the internal transcribed spacer region (rDNA-ITS) and translation elongation factor-1α (TEF-1α) sequences. Optimal growth conditions for A. niger were 30°C, pH 5.0-6.0, and fructose and peptone as carbon and nitrogen sources. The effects of sodium bicarbonate (SBC), natamycin (NT), and combined treatments on A. niger inhibition were investigated. Treatment with 4.0 g/L sodium bicarbonate (SBC) + 5.0 mg/L natamycin (NT) inhibited mycelial growth and spore germination as completely as 12.0 mg/L SBC or 25.0 mg/L NT. SBC and NT treatments disrupted the structural integrity of cell and mitochondria membranes and decreased enzyme activities involved in the tricarboxylic acid (TCA) cycle, mitochondrial membrane potential (MMP), ATP production in mitochondria, and ergosterol content in the plasma membrane, thus leading to the inhibition of A. niger growth. Moreover, experimental results in vivo showed that the rot lesion diameter and decay rate of Shengzhou nane fruit treated with SBC and NT were significantly reduced compared with the control. The results suggest that the combination treatment of SBC and NT could be an alternative to synthetic fungicides for controlling postharvest Shengzhou nane decay caused by A. niger.

Background: Older people experience greater morbidity with a corresponding increase in medication use resulting in a potentially higher risk of adverse drug reactions (ADRs). Objectives: The aim of this study was to; 1) determine the prevalence and characteristics of ADR-related hospital admissions among older patients (≥65 years) in Ireland; and 2) identify the risk factors associated with ADR-related hospital admissions. Methods: A cross-sectional study of ADR prevalence in patients aged ≥65 years admitted acutely to hospital in Ireland over a 8 month period (November 2016- June 2017). A multifaceted review of each hospital admission was undertaken to assess the likelihood of an ADR being a reason for admission (cause of admission or contributing to admission) in the context of the patient's medication, clinical conditions, comorbidities and investigations. A number of decision aids were applied by two independent reviewers to assess ADR causality, avoidability and severity. A random sample of patients, determined not to have a suspected ADR on screening, were assigned to a non-ADR control group. Multivariable logistic regression was used to assess the association between potential risk factors for ADR-related admissions compared with non-ADR-related admissions. Results: In total, 3,760 hospital admission episodes (in 3,091 patients) were screened and 377 admissions were considered ADR-related (10.0%, 95% CI 9.1%, 11.0%). 219 (58.1%) ADR-related admissions were caused by an ADR, while ADRs contributed to 158 (41.9%) admissions. 268 (71.1%) of all ADR-related admissions were deemed definitely or possibly preventable/avoidable. 350 (92.8%) ADRs were classified as being of moderate severity, with 27 (7.2%) classified as severe. Antithrombotic agents, mainly aspirin and warfarin, were the drugs most frequently associated with ADR-related admissions (gastrointestinal and vascular haemorrhagic disorders). In multivariable analysis, immobility, frailty, having delirium or ulcer disease and taking anticoagulant and antiplatelet medication on admission were significantly associated with an ADR-related hospital admission. Conclusion: One in ten hospital admissions, among those aged 65 + years, were considered ADR-related, with approximately 70% potentially avoidable. Reliable and validated ADR detection and prediction tools are needed to develop prevention strategies.

Sperm storage by females after mating for species-dependent periods is used widely among animals with internal fertilization to allow asynchrony between mating and ovulation. Many mammals store sperm in the lower oviduct where specific glycans on epithelial cells retain sperm to form a reservoir. Binding to oviduct cells suppresses sperm intracellular Ca 2+ and increases sperm longevity. We investigated the mechanisms by which a specific oviduct glycan, 3-O-sulfated Lewis X trisaccharide (suLe X ), prolongs the lifespan of porcine sperm. Using targeted metabolomics, we report that binding to suLe X diminishes the abundance of the precursor to ubiquinone and suppresses formation of fumarate, a specific citric acid cycle component, diminishing the activity of the electron transport chain and reducing the production of harmful reactive oxygen species (ROS). The enhanced sperm lifespan in the oviduct may be due to suppressed ROS production as many reports have demonstrated toxic effects of high ROS concentrations on sperm.

Pain is one of the most common reasons for seeking medical intervention, and self-medication with over-the-counter medications and/or traditional herbal remedies has become increasingly popular. In this review, original articles on understanding possible herb-drug interaction between traditional herbs and four major pain medication: acetaminophen, aspirin, ibuprofen, and naproxen were compiled and analyzed. In terms of analytical methods, high-performance liquid chromatography using an isocratic eluent system coupled to biological sample clean-up is the most common, while a wide variety of detectors have been observed, including a photo diode array, variable wavelength detector, electrochemical detector, and tandem mass spectrometer. Both synergistic and anti-synergistic effects were observed for acetaminophen and aspirin, while only synergistic effects have been found for naproxen. Currently, no interactions have been reported for ibuprofen.

Severe heat stress can cause human and animal heart failure and sudden death, which is an important issue of public health worldwide. Our previous studies in animals showed that myocardial cells injury was critical in the above process, and Hsp90 induction has a definite anti-myocardial injury effect, especially through aspirin (ASA). But the mechanism has not been fully clarified. In this study, an in vitro heat stress model of chicken primary myocardial cells (CPMCs) most sensitive to heat stress was used to explore the cell injuries and corresponding molecular resistance mechanism. We found that heat stress resulted in serious oxidation stress and calcium overload in mitochondria, which destroyed the mitochondrial structure and function and then triggered the cell death mechanism of CPMCs. Hsp90 was proven to be a central regulator for resisting heat-stress injury in CPMCs mitochondria using its inhibitor and inducer (geldanamycin and ASA), respectively. The mechanism involved that Hsp90 could activate Akt and PKM2 signals to promote Bcl-2 translocation into mitochondria and its phosphorylation, thereby preventing ROS production and subsequent cell apoptosis. In addition, Hsp90 inhibited mitochondrial calcium overload to overcome MPTP opening and MMP suppression through the inhibitory effect of Raf-1-ERK activation on the CREB-IP3R pathway. This study is the first to reveal a pivotal reason for heat-stressed damage in chicken myocardial cells at subcellular level and identify an effective regulator, Hsp90, and its protective mechanism responsible for maintaining mitochondrial homeostasis.

Rechargeable materials for the effective protection of dry food products were developed. β-cyclodextrin-thymol inclusion complex was covalently grafted on a solid platform of polyethylene terephthalate-viscose using either traditional cross-linker of epichlorohydrin, or natural cross-linker of citric acid. A correlation between the grafting method and physicochemical properties, loading capacity and release capabilities of the resulted materials was studied. The developed materials demonstrated antimicrobial properties preventing mold propagation in wheat grains. The treated grains showed normal germination abilities verifying that the prepared materials can protect dry food products without using harmful chemicals. The suggested approach can be extended to other applications and active agents. A combination of rechargeable films with natural volatiles can serve as an effective platform for sustainable active materials for food protection and in other fields such as agriculture, cosmetics, and medicine.

The molecular mechanisms of opium action with regard to coronary artery disease (CAD) have not yet been determined. The aim of this study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in CAD patients with and without opium addiction. This case-control study was conducted on three groups: (1) opium-addicted CAD patients (CAD + OA, n = 30); (2) CAD patients with no opium addiction (CAD, n = 30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n = 17). The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by the flow cytometry and quantitative polymerase chain reaction (RT-qPCR) methods, respectively. The consumption of atorvastatin, aspirin, and glyceryl trinitrate was found be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD + OA group than in the CAD and Ctrl groups (p = 0.001 and p = 0.005, respectively). MDA levels significantly increased in CAD and CAD + OA patients in comparison with the Ctrl group (p = 0.010 and p = 0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

The antiplatelet effect of polyunsaturated fatty acids is primarily attributed to its metabolism to bioactive metabolites by oxygenases, such as lipoxygenases (LOX). Platelets have demonstrated the ability to generate 15-LOX-derived metabolites (15-oxylipins); however, whether 15-LOX is in the platelet or is required for the formation of 15-oxylipins remains unclear. This study seeks to elucidate whether 15-LOX is required for the formation of 15-oxylipins in the platelet and determine their mechanistic effects on platelet reactivity. In this study, 15-HETrE, 15-HETE, and 15-HEPE attenuated collagen-induced platelet aggregation, and 15-HETrE inhibited platelet aggregation induced by different agonists. The observed anti-aggregatory effect was due to the inhibition of intracellular signaling including αIIbβ3 and protein kinase C activities, calcium mobilization, and granule secretion. While 15-HETrE inhibited platelets partially through activation of peroxisome proliferator-activated receptor β (PPARβ), 15-HETE also inhibited platelets partially through activation of PPARα. 15-HETrE, 15-HETE, or 15-HEPE inhibited 12-LOX in vitro, with arachidonic acid as the substrate. Additionally, a 15-oxylipin-dependent attenuation of 12-HETE level was observed in platelets following ex vivo treatment with 15-HETrE, 15-HETE, or 15-HEPE. Platelets treated with DGLA formed 15-HETrE and collagen-induced platelet aggregation was attenuated only in the presence of ML355 or aspirin, but not in the presence of 15-LOX-1 or 15-LOX-2 inhibitors. Expression of 15-LOX-1, but not 15-LOX-2, was decreased in leukocyte-depleted platelets compared to non-depleted platelets. Taken together, these findings suggest that 15-oxylipins regulate platelet reactivity; however, platelet expression of 15-LOX-1 is low, suggesting that 15-oxylipins may be formed in the platelet through a 15-LOX-independent pathway.

The wrinkled pepper (Capsicum annuum L.) is a type of chili pepper domesticated in northwestern China, with a characteristic flavor. Fifteen wrinkled and four smooth-skinned pepper varieties were evaluated for morphology, texture, color, nutrients, capsaicinoids, and volatile compounds at the mature fruit stage. The sensory evaluation showed wrinkled pepper was superior to smooth pepper in texture, and it has a highly significant correlation (p < 0.01) with cuticle thickness, maximum penetrating force, lignin content, and moisture content. Citric acid was the major organic acid in peppers, accounting for 39.10-63.55% of the total organic acids, followed by quininic acid. The average oxalic acid content of smooth peppers was 26.19% higher than that of wrinkled peppers. The pungency of wrinkled pepper fruits ranged from 1748.9 to 25529.4 SHU, which can be considered slightly to very spicy, while the four smooth varieties ranged between 866.63 and 8533.70 SHU, at slightly to moderately spicy. A total of 199 volatile compounds were detected in the 19 pepper varieties. The average volatile content of wrinkled pepper was 39.79% higher than that of smooth pepper. Twenty-nine volatile compounds, including 14 aldehydes, four alcohols, three esters, three ketones, two furans, one pyrazine, one acid, and one phenol, contributed to the fragrance of peppers and could be regarded as aroma-active compounds, with 2-isobutyl-3-methoxypyrazine being the major contributor among the 19 pepper varieties. Wrinkled pepper can be confidently distinguished from smooth pepper and is of superior quality. The current findings outlined the major texture-related characteristics of pepper as well as the main aroma-active compounds, providing valuable information for pepper quality breeding and consumer guidelines.

Background: Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This systematic review and meta-analysis aimed to explore the efficacy and safety of the concomitant use of PPIs with aspirin-clopidogrel DAPT in patients with Coronary heart disease (CHD). Method: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 2022 for eligible studies. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Subgroup analysis was conducted according to different PPI subtypes, populations, follow-up times and study types. This study was registered on PROSPERO (CRD42022332195). Results: A total of 173,508 patients from 18 studies [2 randomized controlled trials (RCTs), 3 post hoc analyses of RCTs, and 13 cohort studies] were included in this study. Pooled data revealed that coadministration of PPIs significantly increased the risk of major adverse cardiovascular events (MACEs) (HR = 1.15, 95% CI = 1.06-1.26, p = .001) and reduced the risk of gastrointestinal (GI) complications (HR = 0.44, 95% CI = 0.30-0.64, p < .0001). Subgroup analysis results showed that the esomeprazole users and patients with coronary stenting in the PPI group were associated with an increased risk of MACEs compared with the non-PPI group. The occurrence of MACEs in PPI users was more common than that in non-PPI users in long-term follow-up (≥12 months) studies and in the observational studies. There was no significant differences in the incidences of net clinical adverse events (NACEs), all-cause mortality, or cardiac death between the two groups. Conclusion: In patients with CHD, the concomitant use of PPIs with aspirin and clopidogrel was associated with a reduced risk of GI complications but could increase the rates of MACEs (particularly in patients receiving esomeprazole or with coronary stenting). There was no clear evidence of an association between PPI use and NACEs, all-cause mortality, or cardiac death. The results could have been affected by the follow-up time and study type. Further large-scale RCTs with long-term follow-up are needed.

Oryza Sativa is one of the most important food crops in China, which is easily affected by drought during its growth and development. As a member of the calcium signaling pathway, CBL-interacting protein kinase (CIPK) plays an important role in plant growth and development as well as environmental stress. However, there is no report on the function and mechanism of OsCIPK17 in rice drought resistance. We combined transcriptional and metabonomic analysis to clarify the specific mechanism of OsCIPK17 in response to rice drought tolerance. The results showed that OsCIPK17 improved drought resistance of rice by regulating deep roots under drought stress; Response to drought by regulating the energy metabolism pathway and controlling the accumulation of citric acid in the tricarboxylic acid (TCA) cycle; Our exogenous experiments also proved that OsCIPK17 responds to citric acid, and this process involves the auxin metabolism pathway; Exogenous citric acid can improve the drought resistance of overexpression plants. Our research reveals that OsCIPK17 positively regulates rice drought resistance and participates in the accumulation of citric acid in the TCA cycle, providing new insights for rice drought resistance.

Lymphoma is the most common hemopoietic neoplasia in horses. Common clinicopathologic abnormalities in equine lymphoma include hyperglobulinemia, hypoalbuminemia, hyperfibrinogenemia, anemia, thrombocytopenia and lymphocytosis. Hypoglobulinemia has been reported in other species with lymphoma, however it has not been well-described in horses. The objectives of this study were to examine the prevalence of hypoglobulinemia in equine lymphoma, and to identify prognosis and clinicopathological abnormalities associated with serum globulin concentrations.

Objective: This study aimed to explore the effectiveness of sodium bicarbonate (SB) administration on mortality in septic patients with acute moderate lactic acidosis (MLA). Methods: The large ICU database (MIMIC-IV) was retrospectively analyzed. Patients with sepsis and acute MLA were identified. Propensity score analysis (PSA) was performed to explain baseline differences in the probability of accepting or not accepting SB. The edge structured cox model (MSCM) was used to adjust for baseline and time-varying confounding variables. The primary outcome was the ICU and hospital mortality. The subgroup of septic shock was also investigated. Results: A total of 512 septic patients with acute MLA were identified in this study, including 160 in the SB group and 352 in the non-SB group. In the PSA, SB administration was associated with reduced ICU (HR .58, 95% CI 0.38-.89; p <.05) and hospital (HR .67, 95% CI 0.47-.95; p <.05) mortality in septic patients with acute MLA. In the subgroup, the results were similar with septic patients. In the MSCM, SB administration could also improve the ICU (HR .35, 95% CI 0.16-.75; p <.01) and (HR .50, 95% CI 0.28-.88; p <.05) mortality on septic patients. However, In the subgroup, SB administration could only be found associated with improved hospital (HR .44, 95% CI 0.20-.97; p <.05) survival in septic shock. Conclusion: SB administration treatment could reduce ICU and hospital mortality of septic patients with acute MLA. Meanwhile, it could also improve hospital survival in the subgroup of septic shock patients with acute MLA.