Comparative analysis of phenolic compounds in different thinned unripe kiwifruits and their biological functions.

Thinned unripe kiwifruits (TUK) are considered the major agro by-products in kiwifruit production. To promote their potential applications, polyphenols and biological effects of unripe fruits from nine commercial kiwifruit cultivars were compared. Our findings showed that TUK were rich in bioactive polyphenols, which varied greatly by different cultivars. Indeed, catechin, epicatechin, procyanidin PB1, procyanidin B2, protocatechuic acid, neochlorogenic acid, and gallic acid were measured as the major phenolic components in most TUK, with the highest levels observed in 'Hongao' and 'Cuiyu' cultivars. Furthermore, TUK exerted strong in vitro antioxidant capacities, inhibitory effects on digestive enzymes, and anti-inflammatory activities. Particularly, their stronger antioxidant effects and inhibitory effects on digestive enzymes were probably attributed to their higher contents of phenolic compounds, especially procyanidin B2. Collectively, our findings reveal that TUK are potential resources of valuable polyphenols, which can be exploited as natural antioxidants and natural inhibitors of α-glucosidase and α-amylase.

Investigation of the α9-nicotinic receptor single nucleotide polymorphisms induced oncogenic properties and molecular mechanisms in breast cancer.

α9-nAChR, a subtype of nicotinic acetylcholine receptor, is significantly overexpressed in female breast cancer tumor tissues compared to normal tissues. Previous studies have proposed that specific single nucleotide polymorphisms (SNPs) in the CHRNA9 (α9-nAChR) gene are associated with an increased risk of breast cancer in interaction with smoking. The study conducted a breast cancer risk assessment of the α9-nAChR SNP rs10009228 (NM_017581.4:c.1325A > G) in the Taiwanese female population, including 308 breast cancer patients and 198 healthy controls revealed that individuals with the heterozygous A/G or A/A wild genotype have an increased susceptibility to developing breast cancer in the presence of smoking compared to carriers of the G/G variant genotype. Our investigation confirmed the presence of this missense variation, resulting in an alteration of the amino acid sequence from asparagine (N442) to serine (S442) to facilitate phosphorylation within the α9-nAchR protein. Additionally, overexpression of N442 (A/A) in breast cancer cells significantly enhanced cell survival, migration, and cancer stemness compared to S442 (G/G). Four-line triple-negative breast cancer patient-derived xenograft (TNBC-PDX) models with distinct α9-nAChR rs10009228 SNP genotypes (A/A, A/G, G/G) further demonstrated that chronic nicotine exposure accelerated tumor growth through sustained activation of the α9-nAChR downstream oncogenic AKT/ERK/STAT3 pathway, particularly in individuals with the A/G or A/A genotype. Collectively, our study established the links between genetic variations in α9-nAChR and smoking exposure in promoting breast tumor development. This emphasizes the need to consider gene-environment interactions carefully while developing effective breast cancer prevention and treatment strategies.

Glycosylated AIE-active Red Light-triggered Photocage with Precisely Tumor Targeting Capability for Synergistic Type I Photodynamic Therapy and CPT Chemotherapy.

Photocaging is an emerging protocol for precisely manipulating spatial and temporal behaviors over biological activity. However, the red/near-infrared light-triggered photolysis process of current photocage is largely singlet oxygen (1O2)-dependent and lack of compatibility with other reactive oxygen species (ROS)-activated techniques, which has proven to be the major bottleneck in achieving efficient and precise treatment. Herein, we reported a lactosylated photocage BT-LRC by covalently incorporating camptothecin (CPT) into hybrid BODIPY-TPE fluorophore via the superoxide anion radical (O2-•)-cleavable thioketal bond for type I photodynamic therapy (PDT) and anticancer drug release. Amphiphilic BT-LRC could be self-assembled into aggregation-induced emission (AIE)-active nanoparticles (BT-LRCs) owing to the regulation of carbohydrate-carbohydrate interactions (CCIs) among neighboring lactose units in the nanoaggregates. BT-LRCs could simultaneously generate abundant O2-• through the aggregation modulated by lactose interactions, and DNA-damaging agent CPT was subsequently and effectively released. Notably, the type I PDT and CPT chemotherapy collaboratively amplified the therapeutic efficacy in HepG2 cells and tumor-bearing mice. Furthermore, the inherent AIE property of BT-LRCs endowed the photocaged prodrug with superior bioimaging capability, which provided a powerful tool for real-time tracking and finely tuning the PDT and photoactivated drug release behavior in tumor therapy.

Protein disulfide isomerase plays a crucial role in mediating chemically-induced, glutathione depletion-associated hepatocyte injury in vitro and in vivo.

Recently we have shown that protein disulfide isomerase (PDI or PDIA1) is involved in mediating chemically-induced, glutathione (GSH) depletion-associated ferroptotic cell death through NOS activation (dimerization) and NO accumulation. The present study aims to determine the role of PDI in mediating chemically-induced hepatocyte injury in vitro and in vivo and whether PDI inhibitors can effectively protect against chemically-induced hepatocyte injury. We show that during the development of erastin-induced ferroptotic cell death, accumulation of cellular NO, ROS and lipid-ROS follows a sequential order, i.e., cellular NO accumulation first, followed by accumulation of cellular ROS, and lastly cellular lipid-ROS. Cellular NO, ROS and lipid-ROS each play a crucial role in mediating erastin-induced ferroptosis in cultured hepatocytes. In addition, it is shown that PDI is an important upstream mediator of erastin-induced ferroptosis through PDI-mediated conversion of NOS monomer to its dimer, which then leads to accumulation of cellular NO, ROS and lipid-ROS, and ultimately ferroptotic cell death. Genetic manipulation of PDI expression or pharmacological inhibition of PDI function each can effectively abrogate erastin-induced ferroptosis. Lastly, evidence is presented to show that PDI is also involved in mediating acetaminophen-induced liver injury in vivo using both wild-type C57BL/6J mice and hepatocyte-specific PDI conditional knockout (PDIfl/fl Alb-cre) mice. Together, our work demonstrates that PDI is an important upstream mediator of chemically-induced, GSH depletion-associated hepatocyte ferroptosis, and inhibition of PDI can effectively prevent this injury.

Cas12a and MAD7, genome editing tools for breeding.

Food shortages due to population growth and climate change are expected to occur in the near future as a problem that urgently requires solutions. Conventional breeding techniques, notably crossbreeding and mutation breeding, are known for being inefficient and time-consuming in obtaining seeds and seedlings with desired traits. Thus, there is an urgent need for novel methods for efficient plant breeding. Breeding by genome editing is receiving substantial attention because it can efficiently modify the target gene to obtain desired traits compared with conventional methods. Among the programmable sequence-specific nucleases that have been developed for genome editing, CRISPR-Cas12a and CRISPR-MAD7 nucleases are becoming more broadly adopted for the application of genome editing in grains, vegetables and fruits. Additionally, ST8, an improved variant of MAD7, has been developed to enhance genome editing efficiency and has potential for application to breeding of crops.

Sushi Domain Containing 2 Dysfunction Contributes to Cancer Progression in Patients with Bladder Cancer.

Bladder cancer is the most prevalent type of cancer in Taiwan, and therefore, enhancing the diagnostic sensitivity of biomarkers for early-stage tumors and identifying therapeutic targets to improve patient survival rates are essential. Although Sushi Domain Containing 2 (SUSD2) dysfunction has been identified in several types of human cancer, its biological role in bladder cancer remains unclear. Analysis of The Cancer Genome Atlas revealed significantly higher expression of SUSD2 mRNA in bladder cancer tissues than in adjacent normal tissues. This elevated expression of SUSD2 significantly correlated with pathological stage (p = 0.029), pN stage (p < 0.001), and pM stage (p = 0.047). Univariate analysis revealed that high SUSD2 expression was associated with decreased overall survival (crude hazard ratio = 1.70, 95% confidence interval = 1.13-2.56, p = 0.01). Multivariate analysis revealed a significant correlation between high SUSD2 expression and poor survival outcomes (adjusted hazard ratio = 1.53, 95% confidence interval = 1.01-2.31, p = 0.043). IHC analysis revealed a significant correlation between elevated SUSD2 protein levels and unfavorable pathological stages (p < 0.001). SUSD2 suppression significantly reduced the proliferation, colony formation, and invasion of bladder cancer cells. In addition, cell cycle analysis revealed that SUSD2 knockdown induced G2/M phase arrestin bladder cancer cells. Tumor Immune Estimation Resource analysis indicated that expression of SUSD2 was significantly associated with macrophage infiltration and M2 macrophage polarization in bladder cancer. In addition, miR-383-5p directly targeted the 3'UTR of SUSD2, with its ectopic expression inhibiting the growth and motility of bladder cancer cells. Our study revealed that miR-383-5p/SUSD2 axis dysfunction may contribute to a poor prognosis for bladder cancer by affecting cell growth, metastasis, and the tumor microenvironment.

Neutrophils Recruited by NKX2-1 Suppression via Activation of CXCLs/CXCR2 Axis Promote Lung Adenocarcinoma Progression.

NK2 Homeobox 1 (NKX2-1) is a well-characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2-1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2-1 is observed in high-grade LUAD. Meanwhile, single-cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell-cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2-1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT-PCR. ATAC-seq revealed the restrictive regulation of NKX2-1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2-1 modulates the infiltration of tumor-promoting neutrophils by inhibiting CXCLs/CXCR2-dependent mechanisms. Hence, targeting CXCR2 in NKX2-1-low tumors is a potential antitumor therapy that may improve LUAD patient outcomes.

Half-dose ticagrelor versus standard-dose clopidogrel in a dual antiplatelet regimen for stent-assisted coiling or flow diversion of unruptured intracranial aneurysms: a cohort study.

BACKGROUND: Intracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in interventional cardiology. However, the preserved antithrombotic efficacy and better safety of half-dose (45 mg twice daily) ticagrelor remains unverified in patients undergoing stent-assist coiling (SAC) or flow diversion (FD) treating unruptured intracranial aneurysms (UIA). METHODS: A single-center, prospective, cohort study was conducted to compare DAPT with aspirin 100 mg daily plus half-dose ticagrelor vs standard-dose clopidogrel (75 mg daily) in UIA patients. The adenosine diphosphate inhibition (ADPi) rate was utilized to quantify the antagonization of adenosine diphosphate (ADP)-induced platelet aggregation. The patients were followed-up at 6 month after discharge. The primary efficacy outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), and the primary safety outcome was major bleeding. The secondary outcome was minor hemorrhage. RESULTS: Our study included 322 UIA patients, of which 254 patients were eventually enrolled after propensity score matching. The ADPi of half-dose ticagrelor (51.56%±31.46%) was comparable (P=0.089) to that of clopidogrel (57.44%±22.76%). The outcomes were also comparable. Five (3.94%) patients in the ticagrelor group and eight (6.30%) patients in the clopidogrel group reported MACCE (P=0.393). One patient in the ticagrelor group was diagnosed with asymptomatic intracranial hemorrhage 1 month after stenting. There were 36 (28.35%) minor hemorrhagic events in the ticagrelor group and 35 (27.56%) in the clopidogrel group, (P=0.889). CONCLUSION: Half-dose ticagrelor was effective and safe as a potential alternative to clopidogrel in the DAPT regimen for patients undergoing SAC/FD for UIA.

Stigmatization and Preferences in Monkeypox Vaccine Regimens.

A significant monkeypox (mpox) outbreak occurred in 2022, particularly involving sexual and gender minority (SGM) groups. Stigma and misperceptions have led to fear of being labeled a member of the SGM group when obtaining immunization for mpox. We hypothesized that the most recommended injection site, intradermal injection in the forearm, stresses stigmatization. We conducted an online survey in a medical center in Taiwan between May 2023 and June 2023 among adults who were going to receive the second preexposure vaccination. The questionnaire comprised questions about physical and psychological impacts of the first mpox vaccination and the preference for the second vaccination location and factors influencing the preference. A total of 2,827 individuals (98.4% male) completed the questionnaires. Intradermal injection in the forearm was related to greater physical and psychological impacts of local adverse events, especially discoloration. "Beauty," "scar," and "others' view" were the most significant factors influencing preference for vaccination regimens. Compared to intradermal injection in the forearm, subjects who cared about "others' views" were likely to prefer vaccination in the deltoid. The odds ratio for preferring intradermally injection in the deltoid over in the forearm was 1.88 (95% CI 1.38-2.56). The odds ratio for preferring subcutaneous injection in the deltoid over intradermally injection in the forearm was 1.69 (95% CI 1.23-2.32). The odds ratio for preferring intradermally injection in the deltoid regardless of the route over intradermally injection in the forearm was 2.11 (95% CI 1.53-2.92). This study demonstrated the adverse events of different mpox vaccination regimens and their association with stigma. Recognizing the factors affecting the preference for mpox vaccine regimens is crucial for easing the mental stress of vaccinee.

The Anti-Metastatic Action of Oxyresveratrol via Suppression of Phosphoryl-ERK/-PKCα-Mediated Sp1/MMP1 Signaling in Human Renal Carcinoma Cells.

Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki-1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p-ERK/Sp1 and p-PKCα/Sp1-mediated MMP1 expression in RCC.

Investigating the Effectiveness of Electroacupuncture for Diabetic Peripheral Neuropathy and Exploring the Feasibility of Infrared Thermography as an Efficacy Assessment Tool: Study Protocol for a Randomized Controlled Trial.

Introduction: Diabetic peripheral neuropathy (DPN) affects patients' quality of life significantly. To date, selecting the appropriate treatment remains challenging. While electroacupuncture (EA) has shown promise as an effective adjunct therapy for DPN, and infrared thermography (IRT) has been considered as a potential predictor of treatment efficacy, the evidence for both remains inconclusive. As such, the objectives of this trial are twofold: to ascertain the efficacy of EA for DPN, and to explore the feasibility of IRT as an adjunctive objective tool for efficacy assessment. Methods: The study was designed as a randomized, parallel, controlled trial. It spanned over 6 weeks of treatment and an additional 4 weeks of follow-up. 104 eligible participants will be stratified for severity of disease: mild with Toronto clinical scoring system(TCSS) score 6-8, moderate (TCSS score 9-11), and severe (TCSS score 12-19), and each level will be randomised in a 1:1 ratio into a EA group and waiting-list group. The waiting-list group received only the current conventional medication, while the EA group received an additional 12 EA sessions on top of the conventional medication. The primary outcome indicators is nerve conduction velocity (NCV), which will be tested at the baseline and week 6. Total clinical efficiency, TCSS, Clinical symptoms score of Traditional Chinese Medicine (TCM), Patient global impression of change(PGIC), Temperature of regions of interest (ROIs), and Physico chemical examination will be used as secondary outcome indicators. In addition, safety assessment will be determined based on adverse events during the trial. Conclusion: The expected results of this study will determine whether EA improves efficacy in the treatment of DPN with an acceptable safety profile, and investigating variations in the efficacy of EA across different levels of DPN severity. Furthermore, it will explore the viability of IRT as an objective measure for evaluating treatment effectiveness for DPN. Clinical Trial Registration: ClinicalTrials.gov identifier, NCT06054087.

Liposomes with Low Levels of Grafted Poly(ethylene glycol) Remain Susceptible to Destabilization by Anti-Poly(ethylene glycol) Antibodies.

Binding of anti-PEG antibodies to poly(ethylene glycol) (PEG) on the surface of PEGylated liposomal doxorubicin (PLD) in vitro and in rats can activate complement and cause the rapid release of doxorubicin from the liposome interior. Here, we find that irinotecan liposomes (IL) and L-PLD, which have 16-fold lower levels of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG2000 in their liposome membrane as compared to PLD, generate less complement activation but remain sensitive to destabilization and drug release by anti-PEG antibodies. Complement activation and liposome destabilization correlated with the theoretically estimated number of antibody molecules bound per liposome. Drug release from liposomes proceeded through the alternative complement pathway but was accelerated by the classical complement pathway. In contrast to PLD destabilization by anti-PEG immunoglobulin G (IgG), which proceeded by the insertion of membrane attack complexes in the lipid bilayer of otherwise intact PLD, anti-PEG IgG promoted the fusion of L-PLD, and IL to form unilamellar and oligo-vesicular liposomes. Anti-PEG immunoglobulin M (IgM) induced drug release from all liposomes (PLD, L-PLD, and IL) via the formation of unilamellar and oligo-vesicular liposomes. Anti-PEG IgG destabilized both PLD and L-PLD in rats, indicating that the reduction of PEG levels on liposomes is not an effective approach to prevent liposome destabilization by anti-PEG antibodies.

The role of extensive lymph node dissection in the new grading system for lung adenocarcinoma.

OBJECTIVES: This study evaluates the prognostic impact of the new grading system for lung adenocarcinoma, stratified by lymphadenectomy extent. MATERIALS AND METHODS: We analyzed 1258 lung adenocarcinoma patients who underwent curative resections between 2006 and 2017. We analyzed overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) across tumor grades and lymphadenectomy extent, categorized as IASLC-R0 (complete resection) or R(un) (uncertain resection). RESULTS: The median age of cohort was 63 and 41.9 % were male. The majority had undergone lobectomy. The distribution of tumors was 274 grade 1, 558 grade 2, and 426 grade 3 cases. After a median follow-up time of 102 months, the 10-year OS/CSS/RFS rates worsened significantly across grade 1-3: 92.4/99.3/92.3 %, 77.8/87.5/71.7 %, and 63.6/70.2/52.0 %, respectively (p < 0.001). Multivariate Cox regression analysis identified grade 3, R(un) lymphadenectomy, higher Charlson Comorbidity Index, smoking history, thoracotomy, higher pathology stage, and angiolymphatic invasion as independent prognostic factors for lower OS, CSS, and RFS. Furthermore, grade 3 patients benefited significantly from IASLC-R0 lymphadenectomy, showing significantly better OS and RFS than those who underwent R(un) lymphadenectomy (p = 0.007 for OS, p = 0.001 for RFS, post-propensity score matching). Among grade 3 tumors underwent R0 or R(un) resections found the incidence rates of local, distant, and simultaneous local and distant recurrence were 8.5 % vs 13.7 %, 11.0 % vs 12.2 %, and 11.0 % vs 20.6 %, respectively. CONCLUSION: Surgical outcomes for lung adenocarcinoma have declined across grades 1-3. IASLC-R(un) treatment worsens OS and RFS in grade 3. Intensive monitoring and adjuvant therapy should be considered when patients with grade 3 lung adenocarcinoma undergo R(un) lymphadenectomy.

Prognostic Impact of Neoadjuvant Chemotherapy in Localized or Locoregionally Advanced Gallbladder Cancer: A Population-Based and Propensity Score Matched SEER Analysis.

BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.

The nonphototrophic hypocotyl 3 (NPH3) domain protein NRL5 is a trafficking-associated GTPase essential for drought resistance.

The mechanisms of plant drought resistance are unclear but may involve membrane trafficking and metabolic reprogramming, including proline accumulation. Forward genetic screening using a proline dehydrogenase 1 (ProDH1) promoter:reporter identified a drought hypersensitive mutant with a single-amino acid substitution (P335L) in the nonphototrophic hypocotyl 3 (NPH3) domain of NPH3/root phototropism 2-like 5 (NRL5)/naked pins in Yucca 8 (NPY8). Further experiments found that NRL5 and other NPH3 domain proteins are guanosine triphosphatases (GTPases). NRL5, but not NRL5P335L, interacted with the RABE1c and RABH1b GTPases and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) Vesicle-Associated Membrane Protein (VAMP)721/722. These proteins controlled NRL5 localization and connection to trafficking while also being genetically downstream of, and potentially regulated by, NRL5. These data demonstrate that NRL5-mediated restraint of proline catabolism is required for drought resistance and also reveal unexpected functions of the NPH3 domain such that the role of NPH3 domain proteins in signaling, trafficking, and cellular polarity can be critically reevaluated.

IT-DEX and B cell depletion in a child with anti-GAD 65 autoimmune encephalitis presenting as NORSE: A case report.

New-onset refractory status epilepticus (NORSE) is a devastating clinical condition that often leads to severe disability. Intrathecal dexamethasone (IT-DEX) has been reported to improve refractory status epilepticus. We present an 11-year-old female with anti-GAD 65 encephalitis presenting as NORSE who had minimal response to standard anti-seizure medications and first-line immunotherapies. The patient received 6 doses of IT-DEX in conjunction with rituximab which correlated with subsequent decreased neuroinflammation, reduced seizure burden and aided in weaning anesthetic infusions. Our case with literature review suggests IT-DEX may be utilized as an early intervention in those with refractory status epilepticus from various etiologies.

Effects of regulating gut microbiota by electroacupuncture in the chronic unpredictable mild stress rat model.

OBJECTIVE: This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats. METHODS: A total of 40 male Sprague Dawley rats were divided into three groups: normal control, chronic unpredictable mild stress (CUMS), and EA (CUMS + EA). The rats in CUMS and EA groups underwent chronic stress for 10 weeks, and EA group rats received EA treatment for 4 weeks starting from week 7. Body weight and behavioral tests, including the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were monitored. Gut microbiota composition was assessed via 16S rDNA sequencing, and lipid metabolism was analyzed by using UPLC-Q-TOF/MS technology. RESULTS: In comparison to CUMS group, EA could improve the behavior including bodyweight, immovability time, sucrose preference index, crossing piece index and rearing times index. After 4 weeks of EA treatment, 5-HT in hippocampus, serum and colon of depressive rats were simultaneously increased, indicating a potential alleviation of depression-like behaviors. In future studies revealed that EA could regulate the distribution and functions of gut microbiota, and improve the intestinal barrier function of CUMS rats. The regulation of intestinal microbial homeostasis by EA may further affect lipid metabolism in CUMS rats, and thus play an antidepressant role. CONCLUSION: This study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.

Pectic polysaccharides from Tartary buckwheat sprouts: Effects of ultrasound-assisted Fenton treatment and mild alkali treatment on their physicochemical characteristics and biological functions.

Buckwheat sprouts are rich in pectic polysaccharides, which possess numerous health-improving benefits. However, the precise structure-activity relationship of pectic polysaccharides from Tartary buckwheat sprouts (TP) is still scant, which ultimately restricts their applications in the food industry. Hence, both ultrasound-assisted Fenton treatment (UAFT) and mild alkali treatment (MATT) were utilized for the modification of TP, and then the effects of physicochemical characteristics of original and modified TPs on their bioactivities were assessed. Our findings reveled that the UAFT treatment could precisely reduce TP's molecular weight, with the levels decreased from 8.191 × 104 Da to 0.957 × 104 Da. Meanwhile, the MATT treatment could precisely reduce TP's esterification degree, with the values decreased from 28.04 % to 4.72 %. Nevertheless, both UAFT and MATT treatments had limited effects on the backbone and branched chain of TP. Moreover, our findings unveiled that the UAFT treatment could notably promote TP's antioxidant, antiglycation, and immunostimulatory effects, while remarkedly reduce TP's anti-hyperlipidemic effect, which were probably owing to that the UAFT treatment obviously reduced TP's molecular weight. Additionally, the MATT treatment could also promote TP's immunostimulatory effect, which was probably attributed to that the MATT treatment significantly decreased TP's esterification degree. Interestingly, the MATT treatment could regulate TP's antioxidant and antiglycation effects, which was probably attributed to that the MATT treatment simultaneously reduced its esterification degree and bound phenolics. Our findings are conducive to understanding TP's structure-activity relationship, and can afford a scientific theoretical basis for the development of functional or healthy products based on TPs. Besides, the UAFT treatment can be a promising approach for the modification of TP to improve its biological functions.