Development of a specific fluorescent probe to detect advanced glycation end products (AGEs).

Advanced glycation end products (AGEs) play a pivotal role in the aging process, regarded as a hallmark of aging. Despite their significance, the absence of adequate monitoring tools has hindered the exploration of the relationship between AGEs and aging. Here, we present a novel AGE-selective probe, AGO, for the first time. AGO exhibited superior sensitivity in detecting AGEs compared to the conventional method of measuring autofluorescence from AGEs. Furthermore, we validated AGO's ability to detect AGEs based on kinetics, demonstrating a preference for ribose-derived AGEs. Lastly, AGO effectively visualized glycation products in a collagen-based mimicking model of glycation. We anticipate that this study will enhance the molecular tool sets available for comprehending the physiological processes of AGEs during aging.

[Risk Assessment of Antibiotics in Agricultural Environment].

Antibiotics are widely used in animal husbandry, planting, and aquaculture in agricultural industries. A large amount of the parent antibiotics used are released into the environment through discharge via feces and urine, posing potential risks to human health and ecosystems. It is thus very important to understand how antibiotics in the agricultural environment threaten the ecological environment and human health. Accordingly, risk assessment of antibiotics in the environment has become the research focus in recent years. The aim of this study was to review the risk assessment methods of antibiotics. The results showed that the ecological environment risk has mainly been assessed by the risk quotient (RQ). Predicted no-impact concentrations (PNECs) are an important indicator for ecological environment risk assessment, but a definite value is still controversial. The hazard quotient (HQ) is generally used to assess health risks. At present, it is necessary to clarify the selection of antibiotic exposure pathways and toxicological thresholds. However, neither of these two methods have currently considered either mixed pollution or the risk of antibiotic metabolites. Further analysis indicated that the ecological risks of antibiotics in the water environment and feces/manure/soil environment were widespread, which had an impact on both the soil and water environment. The types of antibiotics with high risk were different for various cultivated types. The factors including test species, testing conditions, calculation methods, and soil types all affected the detection of PNECs. Human health risk caused by dietary intake of antibiotics was minimal, but it cannot be ignored given the seafood consumption in coastal areas. Moreover, quinolones have both high ecological and human health risks in the agricultural environment. Based on the amount of antibiotics in agriculture and the residual concentration or toxicity of antibiotics in the related environment, this study proposed a priority-control list of antibiotics in the agricultural environment and summarized the main problems in the current antibiotic risk assessment. It will provide helpful support for the scientific optimization of antibiotic risk assessment and the effective control of antibiotics in agricultural environments.

Research progress on the mechanism of acupuncture on type â ¡ diabetes mellitus. / é’ˆåˆºæ²»ç–—â ¡åž‹ç³–å°¿ç— æ•ˆåº”æœºåˆ¶ç ”ç©¶è¿›å±•.

Acupuncture is an effective measure for treating type 2 diabetes mellitus (T2DM). Many studies have shown that acupuncture can reduce blood glucose in patients with T2DM, but its mechanism is still unclear. This review summarized the mechanism of acupuncture on T2DM, the mechanisms of acupuncture in treating T2DM is related to improving insulin resistance, regulating inflammation, promoting insulin secretion, improving lipid metabolism disorders, resisting oxidative stress, improving obesity, controlling intestinal flora, and regulating the nervous system. At the same time, this review also points out the lack of current relevant research and the future research directions to provide a reference for further exploring the mechanism of acupuncture hypoglycemic action.

Novel Fluorescent Strategy for Discriminating T and B Lymphocytes Using Transport System.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. This observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for the reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury.

We aimed to investigate the neuroprotective effect of rutin on retinal ganglion cells (RGCs) under ischemia-reperfusion (I/R) conditions and the underlying mechanisms involving microglia polarization and JAK/STAT3 signaling. RGCs isolated from C57/Bl6 mice were co-cultured with BV2 microglial cells under normal or in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) conditions. Rutin's effects were evaluated by assessing cell viability, apoptosis rates, cytokine levels, microglial polarization markers and JAK/STAT3 phosphorylation levels. The specific target is confirmed through the inhibitory effect of rutin on the respectively activated signaling factors. Furthermore, molecular docking analyses elucidated rutin-JAK1 interactions. OGD/R conditions significantly reduced RGC viability, exacerbated by BV2 co-culture. However, both 1 µM and 5 µM rutin treatment dose-dependently enhanced RGC viability, reduced apoptosis, and suppressed pro-inflammatory cytokine levels. Western blot analysis indicated that rutin promoted the M2 microglial phenotype and suppressed JAK/STAT3 signaling. Notably, rutin selectively inhibited JAK1 phosphorylation without affecting STAT3. Molecular docking highlighted potential interaction sites between rutin and specific JAK1 pseudokinase domain. Rutin exerts neuroprotective effects against retinal I/R injury by promoting M2 microglial polarization, potentially through the selective inhibition of JAK1 phosphorylation within the JAK/STAT3 signaling pathway. These findings provide a foundation for the therapeutic potential of rutin in retinal I/R injuries.

Prognostic value of systemic immune-inflammation index and monocyte-to-HDL-cholesterol ratio in early cardio-cerebral complications in elderly patients with acute severe carbon monoxide poisoning.

To investigate how effectively systemic immune-inflammation index (SII) and Monocyte-to-HDL-cholesterol ratio (MHR) predict the development of early cardio-cerebral complications in elderly patients who have experienced acute severe carbon monoxide poisoning (ASCMP). A retrospective analysis was conducted on 77 elderly patients with ASCMP admitted to the emergency department of Harrison International Peace Hospital from November 2020 to March 2022. The prevalence of early-onset complications among the 77 individuals was 38.96%. Binary Logistics regression analysis showed that SII and MHR were independent influencing factors of early cardio-cerebral complications in elderly patients with ASCMP. The complication group had a longer length of stay, a greater mortality rate, and a higher incidence of delayed encephalopathy after acute carbon monoxide poisoning (p < .05) than the non-complication group. The area under the curve (AUC) of SII and MHR in predicting early cardio-cerebral complications in elderly patients with ASCMP were 0.724 and 0.796, respectively, with 80.0% and 63.3% sensitivity, and 61.7% and 87.2% specificity. The incidence of early cardio-cerebral complications in elderly patients who had ASCMP is high and the prognosis is poor. SII and MHR can be utilized as independent predictors of early cardio-cerebral complications in elderly patients with ASCMP, allowing doctors to diagnose and treat cardio-cerebral complications earlier and improve prognosis.

Determination of Whole Molecular of Thermostable Direct Hemolysins in Milk Powder by HPLC-ESI-TOF.

Although Vibrio parahaemolyticus (V. parahaemolyticus) is a pathogen frequently found in seafood, there is a possibility of its presence in other foods, such as dairy products. The main virulence factors of V. parahaemolyticus are thermostable direct hemolysins (TDHs) which are lethal toxins, so it is necessary to establish qualitative and quantitative methods for determining TDHs. HPLC-ESI-TOF was employed to establish a method for identifying TDHs. The identification and quantification ions of TDHs were confirmed by HPLC-ESI-TOF. The method was developed for detecting TDHs in milk powder using HPLC-ESI-TOF in this paper, and limits of detection (were between 0.20 and 0.40 mg/kg, limits of quantitation were between 0.5 and 1.0 mg/kg and recoveries of all TDHs were between from 78% to 94% with relative standard deviation lower than 10%. This research will provide a reference for developing methods of HPLC-MS/MS to detect TDHs in food samples, which can provide a tool for the government to monitor TDHs contamination in foods.

Cancer-associated fibroblast exosome LINC00355 promotes epithelial-mesenchymal transition and chemoresistance in colorectal cancer through the miR-34b-5p/CRKL axis.

This study was designed to investigate the role and mechanism of cancer-associated fibroblasts (CAFs)-derived exosomes (CAFs-exo) in metastatic and chemoresistant colorectal cancer (CRC). First, CAFs and normal fibroblasts (NFs) were isolated from CRC tissues and histologically normal adjacent tissues. Then, CAFs-exo and NFs-exo were separated with the help of ultracentrifugation. Next, the morphology, diameter and marker expression of exos were evaluated by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blot, respectively. Besides, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of LINC00355, miR-34b-5p, and CRKL in clinical tissue samples, CRC cells, fibroblasts and exos; MTT assay and cell colony formation assay to assess the chemoresistance and colony formation ability of CRC cells, respectively. Subsequently, the targeting relationship among LINC00355, miR-34b-5p, and CRKL (a target gene of miR-34b-5p) was verified by Luciferase reporter assay; and the binding relationship between LINC00355 and miR-34b-5p was assessed by a pull-down assay. Finally, the expression of epithelial-mesenchymal transition (EMT)-related proteins, and CRKL in cells or exos were detected using western blot. After a series of treatments, CAFs and NFs, CAFs-exo and NFs-exo were successfully isolated and identified. It could be observed that CAFs-exo promoted EMT, colony formation and multidrug resistance in CRC cells by secreting LINC00355. Further studies demonstrated that CAFs-exo-secreted LINC00355 increased the expression of CRKL via inhibiting the expression of miR-34b-5p, thereby enhancing chemoresistance and promoting EMT progression in CRC cells. Collectively, CAFs-exo-derived LINC00355 promotes EMT and chemoresistance in CRC by regulating the miR-34b-5p/CRKL axis.

NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neurons.

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.

Professor GAO Wei-bin's clinical experience of using electroacupuncture for dry eye. / 高维滨电针治疗干眼临床经验撷要.

The academic thoughts of professor GAO Wei-bin regarding the use of electroacupuncture in the treatment of dry eye are introduced. Professor GAO believes that the occurrence of dry eye is mainly related to the stagnation of qi and blood in the eye meridians, leading to inadequate nourishment of the eyes. The acupuncture treatment principle focuses on promoting blood circulation, clearing and benefiting the eye orifices. By integrating traditional acupuncture theory with modern neuroanatomy, the treatment approach centers on stimulating the lacrimal gland, emphasizing the importance of promoting, addressing symptoms as a priority, and considering both the root cause and symptoms.The precise acupoint selection is emphasized. Acupoints of periocular region, such as Taiyang (EX-HN 5) and Leixian point are selected along with Fengchi (GB 20) and Gongxue point to treat dry eye. Attention is also given to the use of electroacupuncture and the selection of its frequencies, emphasizing specific needling techniques based on the severity and classification of the disease.

Measuring the worldwide spread of COVID-19 using a comprehensive modeling method.

BACKGROUND: With the global spread of COVID-19, detecting high-risk countries/regions timely and dynamically is essential; therefore, we sought to develop automatic, quantitative and scalable analysis methods to observe and estimate COVID-19 spread worldwide and further generate reliable and timely decision-making support for public health management using a comprehensive modeling method based on multiple mathematical models. METHODS: We collected global COVID-19 epidemic data reported from January 23 to September 30, 2020, to observe and estimate its possible spread trends. Countries were divided into three outbreak levels: high, middle, and low. Trends analysis was performed by calculating the growth rate, and then country grouping was implemented using group-based trajectory modeling on the three levels. Individual countries from each group were also chosen to further disclose the outbreak situations using two predicting models: the logistic growth model and the SEIR model. RESULTS: All 187 observed countries' trajectory subgroups were identified using two grouping strategies: with and without population consideration. By measuring epidemic trends and predicting the epidemic size and peak of individual countries, our study found that the logistic growth model generally estimated a smaller epidemic size than the SEIR model. According to SEIR modeling, confirmed cases in each country would take an average of 9-12 months to reach the outbreak peak from the day the first case occurred. Additionally, the average number of cases at the peak time will reach approximately 10-20% of the countries' populations, and the countries with high trends and a high predicted size must pay special attention and implement public health interventions in a timely manner. CONCLUSIONS: We demonstrated comprehensive observations and predictions of the COVID-19 outbreak in 187 countries using a comprehensive modeling method. The methods proposed in this study can measure COVID-19 development from multiple perspectives and are generalizable to other epidemic diseases. Furthermore, the methods also provide reliable and timely decision-making support for public health management.

Effect of environmental factors on expression of staphylococcal enterotoxin genes.

Staphylococcal enterotoxins (SEs) secreted by Staphylococcus aureus (S. aureus) can cause foodborne disease, nausea, vomiting and diarrhea, and even death. Regulation of SE expression is related to accessory gene regulators (Agr). It is important to reveal which environmental factors influence regulation of SE expression to prevent SE food poisoning outbreak. Hence, natural environmental factors which may have an impact on SE expression were selected, such as temperature, food types, strains, and competing strains. Seven strains of S. aureus carrying different SE genes were collected from the Chinese Academy of Inspection and Quarantine (CAIQ) strain bank for study. Strains were cultured with different conditions. Temperature was 8 °C, 22 °C, and 30 °C. Food type was milk powder and nutrient broth. Competing strains were Vibrio parahaemolyticus (V. parahaemolyticus), Escherichia coli (E. coli), and Bacillus cereus (B. cereus). The expression culture solution was pretreated by centrifugation, then determined by using SDS-PAGE, and distinguished SEs apart from each other by HPLC-ESI-TOF. There are 168 samples collected from SE expression culture; the result of SDS-PAGE suggests 23 samples were positive for SEs, and the other 145 samples were negative for SEs. The result of HPLC-ESI-TOF suggests that SEs with similar molecular weight can be distinguished in terms of m/z. The most important factor contributing to regulate expression of SEs was estimated by logistic regressive analysis. The result shows that McFadden R2 is 0.213; p value is 0.000 (p < 0.05); this result illustrates that the model is valid and meaningful. Strains, food types, temperature, and competing strands can explain the 21% change in SE expression. Temperature (z = 3.029, p = 0.002 < 0.01), strains (z = - 3.132, p = 0.002 < 0.01), and food types (z = - 2.415, p = 0.016 < 0.05) have significant impact on SE expression, and the competing strains (z = 1.230, p = 0.219 > 0.05) have no impact on the SE expression. More important impact on SE expression was estimated by OR value; the result shows that strength of temperature influencing on SE expression is bigger than strains and food types in terms of values of OR, temperature (OR = 2.862), strains (OR = 0.641), and food types (OR = 0.561); consequently, temperature is a key factor for stimulating SE expression and had high expression at 30 °C. Therefore, food easily contaminated with S. aureus should be monitored intensively at early and late summer, when proper temperature for expressing SEs may result in S. aureus food poisoning prevalence.

[Research progress on the effect mechanism of acupuncture-moxibustion for pressure injuries].

Evidence shows that acupuncture-moxibustion could promote the healing of pressure injuries (PI), but its action mechanism is not fully understood. This review summarizes the basic research literature of acupuncture-moxibustion for PI and identifies that the mechanism of acupuncture-moxibustion for PI is related with regulation of related signaling pathway target proteins, improvement of inflammatory response, modulation of vascular microenvironment, attenuation of oxidative stress damage, and inhibition of cell apoptosis. The review also points out the current limitations and future research directions. It emphasizes the need for further exploration of the upstream regulatory mechanism, specific cellular molecules, and the interactions among these molecules. A multi-level, multi-target, and multi-dimensional approach is required to fully understand the mechanism underlying the promotion of PI healing by acupuncture-moxibustion.

NMN sensor cocktail: selective sensing of nicotinamide mononucleotide over citric acid.

The fluorescent probe pair, NBD-B2 and Styryl-51F, selectively detects NMN over citric acid. NBD-B2 exhibits increased fluorescence, while Styryl-51F shows decreased fluorescence upon NMN addition. Their ratiometric fluorescence change enables highly sensitive and wide-range detection of NMN, effectively distinguishing it not only from citric acid but also other NAD boosters.

Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis.

Patients with ulcerative colitis (UC) have low response rates to anti-integrin medications, necessitating the identification of noninvasive biomarkers for predicting remission to anti-integrin therapy. In this study, patients with moderate to severe UC commencing anti-integrin therapy (n = 29), inactive to mild UC patients (n = 13), and healthy controls (n = 11) were selected. Besides clinical evaluation, fecal samples were collected at baseline and week 14 from moderate to severe UC patients. The clinical remission was defined based on the Mayo score. Fecal samples were assessed with 16S rRNA gene sequencing, liquid chromatography-tandem mass spectrometry, and gas chromatography-mass spectrometry (GC-MS). We identified that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. GC-MS analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared to the nonremission group at baseline. Finally, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961). We identified significantly higher phylum level diversity of Verrucomicrobiota in remission than the nonremission groups at baseline. Notably, the combination of gut microbiome and metabonomic profiles improved the diagnosis of early remission to anti-integrin therapy. IMPORTANCE It is reported that patients with ulcerative colitis (UC) have low response rates to anti-integrin medications in the latest VARSITY study. Therefore, our primary goals were to discover differences in the gut microbiome and metabonomics patterns between early remission and nonremission patients and to explore the diagnostic value in predicting clinical remission to anti-integrin therapy accurately. In this study, we found that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. Gas chromatography-mass spectrometry analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared with the nonremission group at baseline. Notably, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961).

Cortical superficial siderosis, hematoma volume, and outcomes after intracerebral hemorrhage: a mediation analysis.

Background: Previous studies have shown that cortical superficial siderosis (cSS) can increase hematoma volume and predict poor outcomes following primary intracerebral hemorrhage (ICH). Objective: We aimed to determine whether a large hematoma volume was the essential factor contributing to worse outcomes of cSS. Methods: Patients with spontaneous ICH underwent a CT scan within 48 h after ictus. Evaluation of cSS was performed using magnetic resonance imaging (MRI) within 7 days. The 90-day outcome was assessed using the modified Rankin Scale (mRS). In addition, we investigated the correlation between cSS, hematoma volume, and 90-day outcomes using multivariate regression and mediation analyses. Results: Among the 673 patients with ICH [mean (SD) age, 61 (13) years; 237 female subjects (35.2%); median (IQR) hematoma volume, 9.0 (3.0-17.6) ml], 131 (19.5%) had cSS. There was an association between cSS and larger hematoma volume (ß = 4.449, 95% CI 1.890-7.009, p < 0.001) independent of hematoma location and was also related to worse 90-day mRS (ß = 0.333, 95% CI 0.008-0.659, p = 0.045) in multivariable regression. In addition, mediation analyses revealed that hematoma volume was an essential factor mediating the effect of cSS on unfavorable 90-day outcomes (proportion mediated:66.04%, p = 0.01). Conclusion: Large hematoma volume was the major charge of directing cSS to worse outcomes in patients with mild to moderate ICH, and cSS was related to a larger hematoma in both lobar and non-lobar areas. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04803292, identifier: NCT04803292.

Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

[Progress of researches on acupuncture treatment of allergic rhinitis].

Acupuncture therapy has been widely used in clinical treatment of allergic rhinitis (AR), and can induce a positive therapeutic effect through multi-targets and multi-aspects. In recent 10 years, the research on the mechanisms of acupuncture in treating AR mainly focused on humoral immunity, cellular immunity, cell apoptosis, inflammatory mediators and factors, neuropeptides, etc. By regulating the level of immunoglobulin in the blood, acupuncture intervention can restore the relative balance of cellular immune response, reduce the accumulation of eosinophils and promote apoptosis, down-regulate the expression of related inflammatory mediators and factors, regulate the excitability of related nerves, modulate the release of neuropeptides and other ways to diminish the inflammatory reaction of nasal mucosa, and enhance the repair and protection of nasal mucosa, relieve the nasal symptoms at last. On the basis of the existing studies, the follow-up research should make use of the advantages of acupuncture intervention, refine the treatment process, and deeply explore the feasibility of acupuncture treatment of AR, further promote the combination of mechanism study and clinical practice, provide references for clinical application. Moreover, some shortcomings exist, for example, the unknown correlation between the therapeutic effect and duration of treatment, the unknown correlation between the effect of acupuncture and various targets, and disconnection between experimental research achievements and clinical application, etc.

Combining Serum Procalcitonin Level, Thromboelastography, and Platelet Count to Predict Short-term Development of Septic Shock in Intensive Care Unit.

OBJECTIVE: Despite the recent advances in diagnosis and treatment, sepsis continues to lead to high morbidity and mortality. Early diagnosis and prompt treatment are essential to save lives. However, most biomarkers can only help to diagnose sepsis, but cannot predict the development of septic shock in high-risk patients. The present study determined whether the combined measurement of procalcitonin (PCT), thromboelastography (TEG) and platelet (PLT) count can predict the development of septic shock. METHODS: A retrospective study was conducted on 175 septic patients who were admitted to the intensive care unit between January 2017 and February 2021. These patients were divided into two groups: 73 patients who developed septic shock were assigned to the septic shock group, while the remaining 102 patients were assigned to the sepsis group. Then, the demographic, clinical and laboratory data were recorded, and the predictive values of PCT, TEG and PLT count for the development of septic shock were analyzed. RESULTS: Compared to the sepsis group, the septic shock group had statistically lower PLT count and TEG measurements in the R value, K value, α angle, maximum amplitude, and coagulation index, but had longer prothrombin time (DT), longer activated partial thromboplastin time (APTT), and higher PCT levels. Furthermore, the Sequential Organ Failure Assessment (SOFA) score was higher in the septic shock group. The multivariate logistic regression analysis revealed that PCT, TEG and PLT count were associated with the development of septic shock. The area under the curve analysis revealed that the combined measurement of PCT, TEG and PLT count can be used to predict the development of septic shock with higher accuracy, when compared to individual measurements. CONCLUSION: The combined measurement of PCT, TEG and PLT count is a novel approach to predict the development of septic shock in high-risk patients.

Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway.

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo, and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro, these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1ß and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1ß and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.