Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway.

Natural polysaccharides (NPs) possess numerous health-promoting effects, such as liver protection, kidney protection, lung protection, neuroprotection, cardioprotection, gastrointestinal protection, anti-oxidation, anti-diabetic, and anti-aging. Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway is an important endogenous antioxidant pathway, which plays crucial roles in maintaining human health as its protection against oxidative stress. Accumulating evidence suggested that Nrf2 antioxidant pathway might be one of key regulatory targets for the health-promoting effects of NPs. However, the information concerning regulation of NPs on Nrf2 antioxidant pathway is scattered, and NPs show different regulatory behaviors in their different health-promoting processes. Therefore, in this article, structural features of NPs having regulation on Nrf2 antioxidant pathway are overviewed. Moreover, regulatory effects of NPs on this pathway for health-promoting effects are summarized. Furthermore, structure-activity relationship of NPs for health-promoting effects by regulating the pathway is preliminarily discussed. Otherwise, the prospects on future work for regulation of NPs on this pathway are proposed. This review is beneficial to well-understanding of underlying mechanisms for health-promoting effects of NPs from the view angle of Nrf2 antioxidant pathway, and provides a theoretical basis for the development and utilization of NPs in promoting human health.

Prevalence of overweight, obesity, and associated factors among healthcare workers in the Gaza Strip, Palestine: A cross-sectional study.

Background: Overweight and obesity are multifactorial conditions that are prevalent in developing and developed countries. They are emerging as a significant public health concern among healthcare workers (HCWs). We aimed to estimate the prevalence of overweight and obesity and their associated factors among HCWs in the Gaza Strip. Methods: A cross-sectional study was conducted to recruit 1,850 HCWs aged 22 years and older. Interviews were carried out to collect sociodemographic information, nutritional information, and physical activity. Anthropometric measurements [height, weight, and waist circumference] were conducted with the HCWs. The body mass index was computed to determine the prevalence of overweight and obesity. Chi-square, t-test, and one-way ANOVA were used to compare the variables, and logistic regression was used to examine the associated factors of overweight and obesity. Results: The combined prevalence of overweight and obesity among HCWs was 65%. The result of logistic regression showed the risk of being overweight and obesity increased within the age group of 40-49 years (OR = 3.20; 95% CI: 2.37-4.32; P < 0.001). Male participants had more risk of obesity than female participants (OR = 1.77; 95% CI: 1.45-2.15). Married participants had a significantly higher risk of being overweight and obese (OR = 2.52; 95% CI: 2.05-3.28; P = 0.001). Increased monthly income was significantly associated with the risk of being overweight and obese (OR = 2.16; 95% CI: 1.22-3.83; P = 0.008). In addition, hypertension (OR = 2.49; 95% CI: 1.65-3.78; P < 0.001) and type 2 diabetes (OR = 2.42; 95% CI: 1.21-4.85; P= 0.012) were associated with overweight and obesity. Finally, a family history of NCDs was associated with overweight and obesity (OR = 1.69; 95% CI: 1.38-2.07; P < 0.001). Conclusion: This study showed a high prevalence of overweight and obesity among HCWs. Age, monthly income, marital status, known hypertension, type 2 diabetes, and eating habits were associated with the prevalence of overweight and obesity compared to other variables that were not associated with overweight and obesity such as profession, vegetables, fruit consumption, and physical activity. Urgent action is needed to tackle overweight and obesity among HCWs.

Complete Genome Sequence of Staphylococcus capitis CCSM0123, Isolated from Healthy Facial Skin.

Staphylococcus capitis strain CCSM0123 was isolated from healthy facial skin. The complete genome of CCSM0123 was sequenced using a combination of Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) and Illumina sequencing. The assembled 2.5-Mbp genome consisted of one chromosome and four plasmids.

Complete Genome Sequence of Staphylococcus epidermidis CCSM0287, Isolated from Healthy Facial Skin.

Staphylococcus epidermidis strain CCSM0287 was isolated from healthy facial skin. The complete genome of CCSM0287 was sequenced using a combination of Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) and Illumina sequencing. The assembled 2.5-Mbp genome consisted of one chromosome and three plasmids.

Proximity labeling reveals OTUD3 as a DNA-binding deubiquitinase of cGAS.

Cyclic GMP-AMP synthase (cGAS), as the major DNA sensor, initiates DNA-stimulated innate immune responses and is essential for a healthy immune system. Although some regulators of cGAS have been reported, it still remains largely unclear how cGAS is precisely and dynamically regulated and how many potential regulators govern cGAS. Here we carry out proximity labeling of cGAS with TurboID in cells and identify a number of potential cGAS-interacting or -adjacent proteins. Deubiquitinase OTUD3, one candidate identified in cytosolic cGAS-DNA complex, is further validated to not only stabilize cGAS but also enhance cGAS enzymatic activity, which eventually promotes anti-DNA virus immune response. We show that OTUD3 can directly bind DNA and is recruited to the cytosolic DNA complex, increasing its association with cGAS. Our findings reveal OTUD3 as a versatile cGAS regulator and find one more layer of regulatory mechanism in DNA-stimulated innate immune responses.

Reproductive outcomes of women with moderate to severe intrauterine adhesions after transcervical resection of adhesion: A systematic review and meta-analysis.

BACKGROUND: Intrauterine adhesions (IUA) refers to the adhesion of the inner wall of the uterus, resulting in complete or partial occlusion of the uterine cavity, which causes a series of symptoms. Transcervical resection of adhesion (TCRA) is the standard surgical method for patients with IUA. However, the recurrence rate of women with moderate to severe IUA is high and it has raised a big concern about the reproductive outcomes. METHODS: We conducted a scoping review by using 4 databases, including Google Scholar, PubMed, Scopus, Embase, and web of science, to retrieve relevant literature from September 1, 2001, to February 1, 2023, and to explore the reproductive outcomes in women with moderate to severe IUA after TCRA treatment. Following defined guidelines, data extraction was carried out by 2 researchers, and the findings were examined by 2 senior academics. The papers were evaluated by 2 reviewers using the inclusion and exclusion criteria. Using a form developed especially for this study, pertinent information was retrieved, including the first author, research design, study duration, age, intervention measurement, pregnancy rate, techniques of conception, and live birth rate. Two researchers conducted a quality assessment to determine any potential bias using the Cochrane technique and the Newcastle-Ottawa scale. RevMan 5.4.1 (The Cochrane Collaboration, London, United Kingdom) was used for data analysis, while I2 was used to evaluate heterogeneity. RESULTS: In total, this study included 2099 participants. After a detailed systematic review and meta-analyses, the results showed that pregnancy and live birth rates were increased significantly after TCRA, and the risk difference of the pregnancy rate was 1.75 [1.17, 2.62]. Besides, in 2 retrospective studies, the risk difference of live birth rate was 2.26, with a 95% confidence interval of 1.99 to 2.58. Moreover, the menstrual status of women also was improved, and the risk difference of hypermenorrhoea and amenorrhea were -0.28 [-0.37, -0.19] and -0.06 [0.26, 0.13], respectively. CONCLUSIONS: Taken together, TCRA is the useful strategy for the treatment of moderate to severe IUA to enhance the reproductive outcomes in women.

Four-phase computed tomography helps differentiation of renal oncocytoma with central hypodense areas from clear cell renal cell carcinoma.

PURPOSE: To explore the utility of four-phase computed tomography (CT) in distinguishing renal oncocytoma with central hypodense areas from clear cell renal cell carcinoma (ccRCC). METHODS: Eighteen patients with oncocytoma and 63 patients with ccRCC presenting with central hypodense areas were included in this study. All patients underwent four-phase CT imaging including the excretory phases later than 20 min after contrast injection. Two blinded experienced radiologists visually reviewed the enhancement features of the central hypodense areas in the excretory phase images and selected the area demonstrating the greatest degree of enhancement of the tumor in the corticomedullary phase images. Regions of interest (ROIs) were placed in the same location in each of the three contrast-enhanced imaging phases. Additionally, ROIs were placed in the adjacent normal renal cortex for normalization. The ratio of the lesion to cortex attenuation (L/C) for the three contrast-enhanced imaging phases and absolute de-enhancement were calculated. The receiver operating characteristic curve was used to obtain the cut-off values. RESULTS: Complete enhancement inversion of the central areas was observed in 12 oncocytomas (66.67%) and 16 ccRCCs (25.40%) (P = 0.003). Complete enhancement inversion combined with L/C in the corticomedullary phase lower than 1.0 (P < 0.001) or absolute de-enhancement lower than 42.5 HU (P < 0.001) provided 86.42% and 85.19% accuracy, 61.11% and 55.56% sensitivity, 93.65% and 93.65% specificity, 73.33% and 71.43% positive predictive value (PPV), and 89.39% and 88.06% negative predictive value (NPV), respectively, for the diagnosis of oncocytomas. Combined with complete enhancement inversion, L/C in the corticomedullary phase lower than 1.0 and absolute de-enhancement lower than 42.5 HU provided 87.65%, 55.56%, 96.83%, 83.33%, and 88.41% of accuracy, sensitivity, specificity, PPV, and NPV, respectively, for the diagnosis of oncocytomas. CONCLUSION: The combination of enhancement features of the central hypodense areas and the peripheral tumor parenchyma can help distinguish oncocytoma with central hypodense areas from ccRCC.

Brain metabolic signatures in patients with genetic and nongenetic amyotrophic lateral sclerosis.

AIMS: To study the brain metabolic signature in Chinese amyotrophic lateral sclerosis (ALS) patients and compare the difference in brain metabolic patterns between ALS with and without genetic variants. METHODS: We included 146 patients with ALS and 128 healthy controls (HCs). All patients with ALS underwent genetic testing to screen for ALS related genetic variants and were then divided into genetic (n = 22) and nongenetic ALS (n = 93) subgroups. All participants underwent brain 18 F-FDG-PET scans. Group comparisons were performed using the two-sample t-test model of SPM12. RESULTS: We identified a large of hypometabolic clusters in ALS patients as compared with HCs, especially in the bilateral basal ganglia, midbrain, and cerebellum. Moreover, hypometabolism in the bilateral temporal lobe, precentral gyrus and hypermetabolism in the left anterior cingulate, occipital lobe, and bilateral frontal lobe were also found in ALS patients as compared with HCs. Compared with nongenetic ALS patients, genetic ALS patients showed hypometabolism in the right postcentral gyrus, precuneus, and middle occipital gyrus. The incidence of sensory disturbance in patients with genetic ALS was higher than that in patients with nongenetic ALS (5 of 22 [22.72%] vs. 7 of 93 [7.52%], p = 0.036). CONCLUSIONS: Our investigation provided unprecedented evidence of relative hypometabolism in the midbrain and cerebellum in ALS patients. Genetic ALS patients showed a specific signature of brain metabolism and a higher incidence of sensory disturbance, indicating that genetic factors may be an underlying cause affecting the brain metabolism and increasing the risk of sensory disturbance in ALS.

A caprylate esterase-activated fluorescent probe for sensitive and selective detection of Salmonella enteritidis.

Salmonella enteritidis is one of the most common foodborne pathogens. Many methods have been developed to detect Salmonella, but most of them are expensive, time-consuming, and complex in experimental procedures. Developing a rapid, specific, cost-effective, and sensitive detection method is still demanded. In this work, a practical detection method is presented using salicylaldazine caprylate as the fluorescent probe, which could be hydrolyzed by caprylate esterase liberated from Salmonella lysed by phage, to form strong fluorescent salicylaldazine. The Salmonella could be detected accurately with a low limit of detection of 6 CFU/mL and a broad concentration range of 10-106 CFU/mL. Moreover, this method was successfully used for the rapid detection of Salmonella in milk within 2 h through pre-enrichment by ampicillin-conjugated magnetic beads. The novel combination of fluorescent turn-on probe salicylaldazine caprylate and phage ensures this method has excellent sensitivity and selectivity.

Association between anlotinib trough plasma concentration and treatment outcomes in advanced non-small-cell lung cancer.

Background: Efficacy and toxicities of anlotinib (ANL) show large inter-patient variation, which may partly be explained by differences in ANL exposure. Exposure-response/toxicities relationship have not been investigated for ANL. Therefore, the aim of the present study was to explore the association between the trough plasma concentration (Ctrough) of ANL and treatment outcomes in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with advanced NSCLC who started third-line or further ANL alone therapy between January 2021 and October 2022. This study examined the ANL Ctrough and clinical response evaluation at day 43 after initiation of ANL treatment. We evaluated the association between the ANL Ctrough and clinical efficacy and toxicities. Additionally, this study defined patients with complete response (CR), partial response (PR) and stable disease (SD) as responder. The receiver-operating characteristic (ROC) curve combined with Youden index was identify the potential threshold value of ANL Ctrough for the responder. Results: 52 patients were evaluated for analyses. The median ANL Ctrough was 11.45ng/ml (range, 3.69-26.36 ng/ml). The ANL Ctrough values in the PR group (n=6, 15.51 ng/ml (range, 8.19-17.37 ng/ml)) was significantly higher than in the PD group (n=8, 7.44 ng/ml (range, 5.41-14.69 ng/ml), p=0.001). The area under the ROC curve (AUCROC) was 0.76 (95% confidence interval (CI), 0.58-0.93; p=0.022) and threshold value of ANL Ctrough predicting responder was 10.29 ng/ml (sensitivity 65.9% and specificity 87.5%, the best Youden index was 0.53). The disease control rate (DCR) was 84.6%, and DCR was significantly higher in the high-exposure group (≥10.29ng/ml) than low-exposure group (<10.29ng/ml) (96.67% vs 68.18%, p=0.005). Although there was no significant difference in ANL Ctrough between grade ≥ 3 and grade ≤2 toxicities, the incidence of any grade hand-foot syndrome (70.0% vs 36.36%, p=0.016) and thyroid-stimulating hormone elevation (53.33% vs 22.73%, p =0.026) was significantly higher in the high-exposure group compared with the low-exposure group. Conclusions: Considering these results, we propose that maintaining ANL Ctrough ≥ 10.29ng/ml was important for achieving the response in advanced NSCLC patients treated with ANL.

Elevated Urinary IL-6 Predicts the Progression of IgA Nephropathy.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. However, biomarkers for predicting the progression or regression of IgAN remain a clinical challenge. In the present study, we aim to identify promising prognostic markers of IgAN. Methods: Using the cytokine antibody array, we detected serum and urinary levels of 9 common cytokines selected from 23 IgAN-related biomarkers in 32 patients with IgAN and 16 healthy controls. The best biomarkers for distinguishing IgAN patients from healthy controls were identified and confirmed in a multicenter cohort with 222 patients with IgAN and 159 age- and sex-matched healthy controls. Their associations with IgAN progression were further explored in 762 patients with IgAN with a median follow-up of 65 months. Results: Among the 9 candidate markers, urinary interleukin-6 (IL-6) and transforming growth factor-ß1 (TGF-ß1) levels were the best for distinguishing patients with IgAN from healthy controls. In the diagnostic cohort, both urinary IL-6 and TGF-ß1 levels were elevated in patients with IgAN and showed good discriminatory power, with an area under curve (AUC) of 0.9725 (95% confidence interval: 0.9593-0.9858). Elevated urinary IL-6 level was independently and significantly correlated with the high risk of composite renal outcome (hazard ratio per log-transformed IL-6:1.420 [1.139-1.769]), but no statistical significance was observed between urinary TGF-ß1 level and IgAN progression after adjusting for multiple confounders. Conclusions: Elevated urinary IL-6 and TGF-ß1 levels predict the progression of IgAN. Urinary IL-6 is an independent risk factor and a promising noninvasive predictor for IgAN progression.

The interaction between no folic acid supplementation during early pregnancy and preeclampsia increased the risk of preterm birth.

OBJECTIVES: To explore if there is a positive additive interaction between no folic acid (FA) supplementation in early period of pregnancy and preeclampsia which increases the risk of preterm birth (PTB). METHODS: We matched 1471 women who had live-birth singleton preterm infants with 1471 women who had live-birth singleton term infants at 15 Chinese hospitals in 2018. We excluded women who took folic acid less than 0.4 mg/d or less than 12 weeks in early stage, women with gestational hypertension, chronic hypertension, or preeclampsia during previous pregnancy. We calculate odds ratios for PTB by performing conditional logistic regression comparing preterm group with term group.We quantified the interaction between 2 exposures by synergy (S) and relative excess risk due to interaction (RERI). RESULTS: Approximately 40% of preterm cases did not take FA in early pregnancy. After adjusting confounding factors by logistic regression, when the 2 exposures (no early FA supplementation and preeclampsia) co-existed, the risk of all PTB increased significantly (aOR11=12.138; 95% CI 5.726-25.73), the interaction between 2 exposures was positive (S=1.27) and increased 2.385-fold risk of all PTB (RERI=2.385); and there were similar results on iatrogenic PTB (aOR11=23.412; 95% CI 8.882-60.71, S=1.18, RERI=3.347). CONCLUSION: Our multicenter study showed, for the first time, that there was a positive additive interaction between no FA supplementation in early pregnancy and preeclampsia which increased the risk of all PTB, especially iatrogenic PTB.

Mechanical wounds expedited starch degradation in the wound tissues of potato tubers.

Starch degradation occurs rapidly in stressed plants, but it is unclear how starch degradation occurs in potato tubers after they incur mechanical wounding. In this study, we found that wounding significantly upregulated the expression levels of StGWD, StAMY, StBAM, and StISA, and decreased the starch content of potato tubers. Meanwhile, wounding markedly upregulated the expression levels of StSUS, StBG, and StINV genes, and increased the content of sucrose, glucose, and fructose. Furthermore, wounding reduced the proportion of small starch granules and increase that of large as well as medium starch granules, in this way enhancing the average size distribution of starch. Initially, the hard surface layer of starch granules was removed by wounding, but the internal channels and other structures were only slightly affected. Taken together, the results show that wounding can accelerate starch degradation by promoting the accumulation of sucrose, glucose, and fructose, and the hydrolysis of starch granules in potato tubers.

Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/D2R heterodimers.

Growth hormone secretagogue receptor 1a (GHS-R1a) is an important G protein-coupled receptor (GPCR) that regulates a variety of functions by binding to ghrelin. It has been shown that the dimerization of GHS-R1a with other receptors also affects ingestion, energy metabolism, learning and memory. Dopamine type 2 receptor (D2R) is a GPCR mainly distributed in the ventral tegmental area (VTA), substantia nigra (SN), striatum and other brain regions. In this study we investigated the existence and function of GHS-R1a/D2R heterodimers in nigral dopaminergic neurons in Parkinson's disease (PD) models in vitro and in vivo. By conducting immunofluorescence staining, FRET and BRET analyses, we confirmed that GHS-R1a and D2R could form heterodimers in PC-12 cells and in the nigral dopaminergic neurons of wild-type mice. This process was inhibited by MPP+ or MPTP treatment. Application of QNP (10 µM) alone significantly increased the viability of MPP+-treated PC-12 cells, and administration of quinpirole (QNP, 1 mg/kg, i.p. once before and twice after MPTP injection) significantly alleviated motor deficits in MPTP-induced PD mice model; the beneficial effects of QNP were abolished by GHS-R1a knockdown. We revealed that the GHS-R1a/D2R heterodimers could increase the protein levels of tyrosine hydroxylase in the SN of MPTP-induced PD mice model through the cAMP response element binding protein (CREB) signaling pathway, ultimately promoting dopamine synthesis and release. These results demonstrate a protective role for GHS-R1a/D2R heterodimers in dopaminergic neurons, providing evidence for the involvement of GHS-R1a in PD pathogenesis independent of ghrelin.

Increased sympathetic outflow induced by emotional stress aggravates myocardial ischemia-reperfusion injury via activation of TLR7/MyD88/IRF5 signaling pathway.

BACKGROUND AND OBJECTIVE: Emotional stress substantially increases the risk of ischemic cardiovascular diseases. Previous study indicates that sympathetic outflow is increased under emotional stress. We aim to investigate the role of increased sympathetic outflow induced by emotional stress in myocardial ischemia-reperfusion (I/R) injury, and explore the underlying mechanisms. METHODS AND RESULTS: We used Designer Receptors Exclusively Activated by Designer Drugs technique to activate the ventromedial hypothalamus (VMH), a critical emotion-related nucleus. The results revealed that emotional stress stimulated by VMH activation increased sympathetic outflow, enhanced blood pressure, aggravated myocardial I/R injury, and exacerbated infarct size. The RNA-seq and molecular detection demonstrated that toll-like receptor 7 (TLR7), myeloid differentiation factor 88 (MyD88), interferon regulatory factor 5 (IRF5), and downstream inflammatory markers in cardiomyocytes were significantly upregulated. Emotional stress-induced sympathetic outflow further exacerbated the disorder of the TLR7/MyD88/IRF5 inflammatory signaling pathway. While inhibition of the signaling pathway partially alleviated myocardial I/R injury aggravated by emotional stress-induced sympathetic outflow. CONCLUSION: Increased sympathetic outflow induced by emotional stress activates TLR7/MyD88/IRF5 signaling pathway, ultimately aggravating I/R injury.

Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy.

BACKGROUND: Alzheimer Disease (AD) and cerebral amyloid angiopathy (CAA) are both characterized by amyloid-ß (Aß) accumulation in the brain, although Aß deposits mostly in the brain parenchyma in AD and in the cerebrovasculature in CAA. The presence of CAA can exacerbate clinical outcomes of AD patients by promoting spontaneous intracerebral hemorrhage and ischemia leading to CAA-associated cognitive decline. Genetically, AD and CAA share the ε4 allele of the apolipoprotein E (APOE) gene as the strongest genetic risk factor. Although tremendous efforts have focused on uncovering the role of APOE4 on parenchymal plaque pathogenesis in AD, mechanistic studies investigating the role of APOE4 on CAA are still lacking. Here, we addressed whether abolishing APOE4 generated by astrocytes, the major producers of APOE, is sufficient to ameliorate CAA and CAA-associated vessel damage. METHODS: We generated transgenic mice that deposited both CAA and plaques in which APOE4 expression can be selectively suppressed in astrocytes. At 2-months-of-age, a timepoint preceding CAA and plaque formation, APOE4 was removed from astrocytes of 5XFAD APOE4 knock-in mice. Mice were assessed at 10-months-of-age for Aß plaque and CAA pathology, gliosis, and vascular integrity. RESULTS: Reducing the levels of APOE4 in astrocytes shifted the deposition of fibrillar Aß from the brain parenchyma to the cerebrovasculature. However, despite increased CAA, astrocytic APOE4 removal reduced overall Aß-mediated gliosis and also led to increased cerebrovascular integrity and function in vessels containing CAA. CONCLUSION: In a mouse model of CAA, the reduction of  APOE4 derived specifically from astrocytes, despite increased fibrillar Aß deposition in the vasculature, is sufficient to reduce Aß-mediated gliosis and cerebrovascular dysfunction.

miR-183-5p overexpression orchestrates collective invasion in salivary adenoid cystic carcinoma through the FAT1/YAP1 signaling pathway.

The invasion of cancer cells into interstitial tissues in a cohesive unit is termed collective invasion, and it is important for the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). However, the underlying mechanisms regulating SACC collective invasion are still poorly understood. Here, we found that SACC tissues exhibited remarkable FAT1 downregulation and YAP1 upregulation at the invasive front, which was closely associated with collective invasion and distant metastasis. Decreasing FAT1 expression significantly activated the YAP1 signaling pathway and promoted collective invasion. Moreover, miR-183-5p was identified as the candidate regulator of FAT1 by bioinformatic analysis and an online database algorithm. A dual luciferase reporter experiment further confirmed that miR-183-5p directly targeted the FAT1 3'-UTR to reduce FAT1 expression. Increasing or decreasing miR-183-5p expression promoted or attenuated collective invasion, which was reversed by YAP1 siRNA or FAT1 siRNA, respectively. In addition, knocking down miR-183-5p reduced tumor burden and attenuated collective invasion in vivo. Together, these results suggest that the miR-183-5p/FAT1/YAP1 signaling pathway is a critical driver of SACC collective invasion, revealing a novel therapeutic target.

Intestinal prolapse and exposure after peritoneal dialysis in low-birth-weight preterm infants with acute renal failure: a case report.

Background: The mortality rate of acute kidney injury (AKI) in low-birth-weight premature infants with acute renal failure is extremely high. Since small hemodialysis catheters do not exist, peritoneal dialysis (PD) is the most suitable dialysis method. At present, only a few studies have reported cases of PD in low-birth-weight newborns. Case Description: On September 8, 2021, a 10-day-old, low-birth-weight preterm infant, who presented with neonatal respiratory distress syndrome and acute renal failure, was admitted to the Second Affiliated Hospital of Kunming Medical University, China. The patient was the elder of twins and had experienced acute renal failure, hyperkalemia, and anuria following the onset of respiratory distress syndrome. During the initial PD catheterization operation, a double Tenckhoff adult PD catheter cut short by 2 cm was used, with the inner cuff placed in the skin. However, the surgical incision was relatively large, and PD fluid leakage occurred. Later, the incision tore, and the intestines prolapsed when the patient cried. The intestines were returned to the abdominal cavity in an emergency operation, and the PD catheter was placed again. This time, the inner Tenckhoff cuff was placed outside the skin, and PD fluid leakage did not reoccur. However, the patient also experienced a decrease in heart rate and blood pressure, as well as severe pneumonia and peritonitis. Following an active rescue, the patient recovered well. Conclusions: The PD method effectively treats low-birth-weight preterm neonates with AKI. An adult Tenckhoff catheter was shortened by 2 cm and successfully used in the PD treatment of a low-birth-weight preterm infant. However, the catheter placement should be outside the skin, and the incision should be as small as possible to avoid leakage and incision tears.

Anemonin reduces hydrogen peroxide-induced oxidative stress, inflammation and extracellular matrix degradation in nucleus pulposus cells by regulating NOX4/NF-κB signaling pathway.

BACKGROUND: Excessive oxidative stress plays a critical role in the progression of various diseases, including intervertebral disk degeneration (IVDD). Recent studies have found that anemonin (ANE) possesses antioxidant and anti-inflammatory effects. However, the role of ANE in IVDD is still unclear. Therefore, this study investigated the effect and mechanism of ANE on H2O2 induced degeneration of nucleus pulposus cells (NPCs). METHODS: NPCs were pretreated with ANE, and then treated with H2O2. NOX4 was upregulated by transfection of pcDNA-NOX4 into NPCs. Cytotoxicity was detected by MTT, oxidative stress-related indicators and inflammatory factors were measured by ELISA, mRNA expression was assessed by RT-PCR, and protein expression was tested by western blot. RESULTS: ANE attenuated H2O2-induced inhibition of NPCs activity. H2O2 enhanced oxidative stress, namely, increased ROS and MDA levels and decreased SOD level. However, these were suppressed and pretreated by ANE. ANE treatment repressed the expression of inflammatory factors (IL-6, IL-1ß and TNF-α) in H2O2-induced NPCs. ANE treatment also prevented the degradation of extracellular matrix induced by H2O2, showing the downregulation of MMP-3, 13 and ADAMTS-4, 5 and the upregulation of collagen II. NOX4 is a key factor regulating oxidative stress. Our study confirmed that ANE could restrain NOX4 and p-NF-κB. In addition, overexpression of NOX4 counteracted the antioxidant and anti-inflammatory activities of ANE in H2O2-induced NPCs, and the inhibition of the degradation of extracellular matrix induced by ANE was also reversed by overexpression of NOX4. CONCLUSION: ANE repressed oxidative stress, inflammation and extracellular matrix degradation in H2O2-induced NPCs by inhibiting NOX4/NF-κB pathway. Our study indicated that ANE might be a candidate drug for the treatment of IVDD.

Xenon attenuates hypoxic-ischemic brain damage by inhibiting autophagy in neonatal rats.

Xenon (Xe) is an inert, colorless and odorless heavy gas and has many biological functions. However, little is known about whether and how Xe can modulate hypoxic-ischemic brain damage (HIBD) in neonatal rats. This study employed a neonatal rat model to explore the potential effect of Xe on neuron autophagy and the severity of HIBD. Neonatal Sprague-Dawley rats were subjected to HIBD, randomized and treated with Xe or mild hypothermia (at 32 °C) for 3 h. The degrees of HIBD, neuron autophagy and the neuronal functions in some neonates from each group were tested by histopathology, immunochemistry, transmission electron microscopy, western blot, open-field and Trapeze tests at 3 and 28 days post-induction of HIBD, respectively. Compared with the Sham group, hypoxic-ischemia caused larger volumes of cerebral infarction and severe brain damage, and increased autophagosome formation and Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 class II (LC3-II) expression in the brain of rats, accompanied by the defect in neuronal functions. In contrast, treatment with Xe and/or hypothermia significantly reduced infarct volumes and ameliorated neurological defects in the HIBD rats, particularly for the combination of Xe and hypothermia. Xe significantly mitigated the relative levels of Beclin-1 and LC3-II expression and autophagosome formation induced by HIBD in rats. Xe acted as a neuroprotective factor against HIBD, possibly by inhibiting the hypoxia-induced neuron autophagy in rats.