Nobiletin protects enteric nerves and ameliorates disordered bowel motility in diet-induced obese mice via increasing Trem2 expression.

Nobiletin can regulate lipid metabolism and protect the central nervous system. However, its role in the enteric nervous system (ENS) of obese subjects is still unclear. To investigate the ENS protective effects and mechanism of nobiletin in obese mice, male C57BL/6 mice were fed a chow diet and a high-fat diet (HFD) for 8 weeks. The identified obese and control mice were grouped and administered vehicle, nobiletin 40 mg/kg, 100 mg/kg or 200 mg/kg daily for 4 weeks. The major indexes of obesity, intestinal transit rate, PGP9.5, nNOS, TNF-α, IL-1ß, IL-6, IL-10, Bcl2 and Bax were measured. The full-length transcriptome was used to analyze differentially expressed genes (DEGs) in the colon. The results indicated that nobiletin effectively improved major indexes of obesity and bowel motility function, suppressed the expression of TNF-α, IL-1ß, IL-6 and Bax, and upregulated the expression of IL-10, Bcl2, PGP9.5 and nNOS. Based on full-length transcriptome sequencing, nobiletin regulated lipid metabolism and inflammation via the PPAR and NOD-like receptor signaling pathways. Trem2 expression was significantly reduced in obese mice. However, Trem2 expression was significantly increased after nobiletin treatment in obese mice. The enrichment analysis showed that Trem2 plays an important role in enteric neuroinflammation. In conclusion, nobiletin regulates lipid metabolism and inflammation in obese mice. Trem2 is a potential target of nobiletin for ENS protection in obese mice.

Hyperoxia combined with the B-cell antagonist rituximab led to intestinal dysbiosis in neonatal mice.

The adverse factors impacting the intestinal microbiota of newborns remain to be elucidated. We put forward a hypothesis that hyperoxia in combination with rituximab exhibits a synergistic effect that interferes with neonatal intestinal microbiota. Six C57BL/6J mice, aged 12 weeks and pregnant 18 days, were purchased. Their pups were breastfed and raised under a 75% oxygen or conventional environment. Low- (20 mg/kg) and high-dose (40 mg/kg) rituximab were intraperitoneally administered. Fecal genomic DNA was extracted and sequenced by a 16S rRNA platform. Severe intestinal dysbiosis in newborns were observed, whereas mild dysbiosis was caused by inducing hyperoxia alone, confirming the synergistic interference of the combination of hyperoxia and B-cell antagonist (rituximab) in neonatal intestinal microbiota disruption. Slight dysbiosis was observed in the intestinal microbiota of dams, indicating their much robust ability to confront hyperoxic conditions. The abundance of Akkermansia muciniphila was significantly and extensively altered in both pups and dams after being subjecting them to hyperoxic conditions with or without rituximab administration. In conclusion, this work demonstrated that the synergistic effect of hyperoxia and rituximab led to severe intestinal dysbiosis in newborns. More studies are recommended to explore the precise regulatory mode between hyperoxia and rituximab in intestinal microbiota.

Potential novel biomarkers in small intestine for obesity/obesity resistance revealed by multi-omics analysis.

BACKGROUND: Although obesity is caused by different factors, individual susceptibility to obesity differs among people under the same circumstances. The microbiota in the caecum or fresh faeces and metabolites in blood or urine contribute to obesity resistance; however, the microbiota or metabolites in the small intestine have not been extensively studied. METHODS: To investigate the relationship between the microbiota or metabolites in the small intestine and susceptibility to obesity, eighty-eight male C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to establish two models of obesity and obesity resistance. For further study, six mice were chosen from among the obesity models, and twelve mice were randomly chosen from among the obesity resistance models. After fasting plasma glucose and behavioural testing, the mice were fed in single cages for another 4 weeks to observe their weight and food intake. All mice were sacrificed at 20 weeks of age. Serum ALT, AST, HDL, LDL, TG and TC levels were measured using an automatic biochemical analyser. The microbiota and metabolites in the small intestine contents were analysed using 16 S sequencing and an ultrahigh-performance liquid chromatographic system, respectively. Transcripts in the jejunum were evaluated using full-length transcriptome sequencing and verified by qPCR. RESULTS: The results showed that HFD induced depression and anxiety behaviours and higher fasting plasma glucose, ALT, AST, HDL, LDL, TG and TC levels in the obese mice; however, these levels were improved in obese resistance mice. The correlation analysis showed that the phosphatidylcholine, TG, and phosphatidylethanolamine levels were higher in obese mice and correlated positively with intestinal microflora (Desulfovibrio and Gemella) and the Cxcl10 gene. A higher abundance of Clostridium_sensu_stricto_1 in obesity-resistant mice correlated negatively with the metabolite contents (neuromedin N and enkephalin L) and Pck1 gene expression and correlated positively with certain metabolites (5-hydroxy-L-tryptophan, cinnamyl alcohol and 1 H-indole-3-acetamide) and genes expression (Gdf15, Igfbp6 and Spp1). CONCLUSION: Clostridium_sensu_stricto_1, neuromedin N, enkephalin L, Pck1, 5-hydroxy-L-tryptophan, Cxcl10 and cinnamyl alcohol may be novel biomarkers in the small intestine for obesity/obesity resistance. These might be helpful for obesity prevention or for treating obese patients.

Maslinic Acid: A New Compound for the Treatment of Multiple Organ Diseases.

Maslinic acid (MA) is a pentacyclic triterpene acid, which exists in many plants, including olive, and is highly safe for human beings. In recent years, it has been reported that MA has anti-inflammatory, antioxidant, anti-tumor, hypoglycemic, neuroprotective and other biological activities. More and more experimental data has shown that MA has a good therapeutic effect on multiple organ diseases, indicating that it has great clinical application potential. In this paper, the extraction, purification, identification and analysis, biological activity, pharmacokinetics in vivo and molecular mechanism of MA in treating various organ diseases are reviewed. It is hoped to provide a new idea for MA to treat various organ diseases.

Regulating the Enteric Nervous System against Obesity in Mice by Electroacupuncture.

BACKGROUND AND OBJECTIVES: The enteric nervous system (ENS) dominates the onset of obesity and has been shown to regulate nutrient absorption and energy metabolism. METHODS AND STUDY DESIGN: This study was performed to investigate the role of electroacupuncture in regulating ENS function in obese mice. Obese mice were obtained by high-fat diet. 16S rRNA pyrosequencing, Western blotting, quantitative PCR, and neurotransmitter analysis were used for this purpose. RESULTS: Body weight, Lee index, serum lipid, leptin, and adiponectin levels, and other basic indices were significantly ameliorated after electroacupuncture intervention. The pathological ENS scores, serum neurotransmitter levels, and intestinal transit rate were markedly changed in obese mice. Moreover, electroacupuncture promoted the diversity of gut microbiota. No significant differences were observed 21 and 28 days after electroacupuncture. CONCLUSIONS: These results suggested ENS may be a new treatment approach to obesity.

The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology.

Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis. SOI has a serious impact on women's physical and mental health and family harmony, and it is a clinical problem that needs to be solved urgently.

Objective: The purpose of the present study was to explore the potential pharmacological mechanisms of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.

Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed through the STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation, Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of tubal inflammation and to validate the predictions of network pharmacology and the therapeutic efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes. TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected by western blot.

Results: Through database analysis, it was found that YJP shared 105 identical targets with the disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5 core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved. The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue, inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore, YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated ESR1.

Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.

Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture.

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

Melatonin restores DNFB-induced dysbiosis of skin microbiota in a mouse model of atopic dermatitis.

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.

Matrix metalloproteinase activity in early-stage lung cancer.

BACKGROUND: The matrix metalloproteinases (MMPs)-2, -9 and -7 are thought to be associated with tumor invasion, metastasis, and angiogenesis. However, their possible roles in early-stage lung cancer are not clear. We measured the activity of MMP-2, -7 and -9 in early-stage lung cancer tissues. MATERIAL AND METHODS: Normal lung tissues and cancer tissues were collected from 60 consecutive stage-I non-small cell lung cancer (NSCLC) patients. The activities of MMP-2 and MMP-9 were determined by gelatin zymography, and the activity of MMP-7 was determined by casein zymography. Furthermore, the ratio of the active form of MMP-2 in tumor tissue (T) compared with normal tissue (N) was determined, and the survival in the groups with different MMP-2 T:N ratio was compared. RESULTS: The activity of both MMP-2 and MMP-9 was detected in all cancer and normal tissues. Interestingly, MMP-9 activity was significantly reduced, whereas MMP-2 activity was significantly increased, in cancer tissues compared to normal tissues. The survival rate of the MMP-2 T:N ratio > 2.5 group was 57.45%, which was significantly reduced compared with that of the T:N ratio ≤ 2.5 group (86.78%). CONCLUSION: Our findings suggest that MMP-2, but not MMP-9 and MMP-7, may be implicated in early-stage tumor invasion, metastasis, and angiogenesis in NSCLC.

A comparison of anatomical and dosimetric variations in the first 15 fractions, and between fractions 16 and 25, of intensity-modulated radiotherapy for nasopharyngeal carcinoma.

The purpose of this study was to compare anatomical and dosimetric variations in first 15 fractions, and between fractions 16 and 25, during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Twenty-three NPC patients who received IMRT in 33 fractions were enrolled. Each patient had two repeat computed tomography (CT) scans before the 16th and 25th fraction. Hybrid IMRT plans were generated to evaluate the dosimetric changes. There was a significant decrease of the transverse diameter of nasopharyngeal and neck as well as gross tumor volume (GTV) in the primary nasopharyngeal carcinoma (GTVnx) and involved lymph nodes (GTVnd) during the first 15 fractions, and between fraction 16 and 25 (p < 0.05). Consequently, there was a significant reduction of the percentage of the volume receiving the prescribed dose (V100) of CTV1 and GTVnd, which was more prominent after the first 15 fractions treatment compared to that between fraction 16 and 25 (p < 0.05). Additionally, there was a significant increase in the mean dose (Dmean) and percentage of volume receiving ≥ 30 Gy (V30) to the bilateral parotid in the first 15 fractions (p < 0.05), but not between fraction 16 and 25. While the maximum dose to the spinal cord was significantly increased both in the first 15 fractions, and between fraction 16 and 25 (p < 0.05), the increase of the percent of spinal cord volume receiving ≥ 40 Gy (V40) was significantly higher in the first 15 fractions compared to that between fraction 16 and 25 (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, a total 39.1% (9/23) of phantom plan 1 (generated by applying the beam configurations of the original IMRT treatment plan to the anatomy of the second CT scan) and 17.4% (4/23) of phantom 2 (generated by applying the beam configurations of the replan 1 to the anatomy of the third CT scan) were out of limit for the dose to the normal critical structures. In conclusion, our data indicated that anatomic changes resulted in more predominant dosimetric effects in the first 15 fractions, and between fractions 16 and 25, of IMRT.

Effect and mechanism of acupuncture on endogenous and exogenous stem cells in disease treatment: A therapeutic review.

Acupuncture is effective intervention, particularly in nerve, endocrine diseases and immune diseases. The potential mechanisms mediating the effects of acupuncture include anti-inflammatory and oxidative stress, inhibition of cell apoptosis, and stimulation of the proliferation and differentiation of endogenous stem cells. Traditional Chinese medicine combined with stem cell transplantation have a synergistic effect in the treatment of diseases. Increasing studies have found that acupuncture can promote the proliferation, differentiation, homing and survival of exogenous stem cells. This article reviews the mechanism of acupuncture and Chinese herbs on endogenous stem cells and exogenous stem cells in the combined intervention of diverse disorders and the major problems in past 15 years, which will provide a reference for future clinical research.

A review on recent advances on nobiletin in central and peripheral nervous system diseases.

In recent years, the role of nobiletin in neuronal disorders has received extensive attention. However, the study of nobiletin in the peripheral nervous system is limited. Nobiletin, as a compound with high fat solubility, high bioavailability and low toxicity, has been extensively studied. Accumulating scientific evidence has shown that nobiletin has a variety of biological functions in the nervous system, such as inhibiting the expression of inflammatory factors, reducing the neurotoxic response, improving the antioxidant capacity, promoting the survival of nerve cells, promoting axon growth, reducing blood‒brain barrier permeability, reducing brain oedema, promoting cAMP response element binding protein expression, improving memory, and promoting mild depolarization of nerve cell mitochondria to improve antioxidative stress capacity. Accumulating studies have shown that nobiletin also protects enteric nervous system, spinal cord and sciatic nerve. To explore the new therapeutic potential of nobiletin in the nervous system, recent and relevant research progress is reviewed in this article. This will provide a new research idea for nobiletin in the nervous system.

Activation of D1R signaling in the medial prefrontal cortex rescues maternal separation-induced behavioral deficits through restoration of excitatory neurotransmission.

Lack of maternal care and attention during infancy and childhood increases the likelihood of developing a range of neuropsychiatric disorders, such as social deficits, working memory impairment, and anxiety-like behaviors, in adulthood. However, the neuroregulatory signaling through which early-life stress causes behavioral and cognitive abnormalities in the offspring is largely unexplored. Here, we show that in mice, unpredictable maternal separation (MS) during the early postnatal period impairs neuronal development in the medial prefrontal cortex (mPFC) and results in long-lasting behavioral changes. Additionally, MS disrupts excitatory neurotransmission and inhibits the neuronal activity of pyramidal neurons in the mPFC. Differentially expressed gene (DEG) analysis of RNA sequencing (RNA-seq) data of mPFC showed that dopamine D1 receptor (D1R) was significantly downregulated in MS animals. Finally, we show that pharmacological activation of D1R signaling specifically in the mPFC improves neuronal excitability and rescues behavioral and cognitive dysfunction of MS mice, whereas pharmacologically inhibiting of D1R in the mPFC mimics MS-induced behavioral abnormalities in control mice. Together, our results identify D1R signaling in the mPFC, at least in part, as a potential therapeutic target for the behavioral and cognitive abnormalities caused by deprivation of maternal care in early life.

Mitochondria-associated regulation in adipose tissues and potential reagents for obesity intervention.

Introduction: A systematic review analysis was used to assess the profile of mitochondrial involvement in adipose tissue regulation and potential reagents to intervene in obesity through the mitochondrial pathway. Methods: Three databases, PubMed, Web of Science, and Embase, were searched online for literature associated with mitochondria, obesity, white adipose tissue, and brown adipose tissue published from the time of their creation until June 22, 2022, and each paper was screened. Results: 568 papers were identified, of which 134 papers met the initial selection criteria, 76 were selected after full-text review, and 6 were identified after additional searches. A full-text review of the included 82 papers was performed. Conclusion: Mitochondria play a key role in adipose tissue metabolism and energy homeostasis, including as potential therapeutic agents for obesity.

Electroacupuncture activates angiogenesis by regulating the PI3K/Pten/Thbs1 signaling pathway to promote the browning of adipose tissue in HFD-induced obese mice.

This study investigated the effect of electroacupuncture (EA) on the browning of white adipose tissue (WAT) via angiogenesis and its potential mechanism in obese mice. Four-week-old male C56BL/6 mice were randomly divided into a high-fat diet (HFD) and a normal chow diet (ND) group. After 12 weeks, HFD mice were randomly divided into two groups to receive or not receive EA for 3 weeks. After EA treatment, body weight, adipocyte size, serum glucose (GLU), triacylglycerol (TG), cholesterol (CHO), leptin (Lep), monocyte chemoattractant protein-1 (MCP-1), WAT browning-related genes, angiogenesis-related genes, and the PI3K/Pten/Thbs1 signaling pathway were evaluated. The results indicated that EA significantly reduced body weight, adipocyte size, and serum concentrations of GLU, TG, CHO, Lep and MCP-1 and promoted WAT browning. Angiogenesis and the PI3K/Pten/Thbs1 signaling pathway were all activated by EA intervention. The expression levels were consistent with the results of RNA-seq and confirmed via qRTPCR and WB. Our study showed that EA may activate angiogenesis via the PI3K/Pten/Thbs1 signaling pathway in WAT, thereby promoting the browning and thermogenesis of adipose tissue.

Acupuncture ameliorates Mobile Phone Addiction with sleep disorders and restores salivary metabolites rhythm.

Objectives: Mobile Phone Addiction (MPA) is a novel behavioral addiction resulting in circadian rhythm disorders that severely affect mental and physical health. The purpose of this study is to detect rhythmic salivary metabolites in MPA with sleep disorder (MPASD) subjects and investigate the effects of acupuncture. Methods: Six MPASD patients and six healthy controls among the volunteers were enrolled by MPA Tendency Scale (MPATS) and Pittsburgh Sleep Quality Index (PSQI), then the salivary samples of MPASD and healthy controls were collected every 4-h for three consecutive days. Acupuncture was administered for 7 days to MPASD subjects, then saliva samples were collected again. Salivary metabolomes were analyzed with the method of LC-MS. Result: According to our investigation, 70 (57.85%) MPA patients and 56 (46.28%) MPASD patients were identified among 121 volunteers. The symptoms of the 6 MPASD subjects were significantly alleviated after acupuncture intervention. The number of rhythmic saliva metabolites dropped sharply in MPASD subjects and restored after acupuncture. Representative rhythmic saliva metabolites including melatonin, 2'-deoxyuridine, thymidine, thymidine 3',5'-cyclic monophosphate lost rhythm and restored after acupuncture, which may attribute to promising MPASD treatment and diagnosis biomarkers. The rhythmic saliva metabolites of healthy controls were mainly enriched in neuroactive ligand-receptor interaction, whereas polyketide sugar unit biosynthesis was mainly enriched in MPASD patients. Conclusion: This study revealed circadian rhythm characteristics of salivary metabolites in MPASD and that acupuncture could ameliorate MPASD by restoring part of the dysrhythmia salivary metabolites.

Failure patterns of locoregional recurrence after reducing target volumes in patients with nasopharyngeal carcinoma receiving adaptive replanning during intensity-modulated radiotherapy: a single-center experience in China.

BACKGROUND: Previous researches have demonstrated that adaptive replanning during intensity-modulated radiation therapy (IMRT) could enhance the prognosis of patients with nasopharyngeal carcinoma (NPC). However, the delineation of replanning target volumes remains unclear. This study aimed to evaluate the feasibility of reducing target volumes through adaptive replanning during IMRT by analyzing long-term survival outcomes and failure patterns of locoregional recurrence in NPC. METHODS: This study enrolled consecutive NPC patients who received IMRT at our hospital between August 2011 and April 2018. Patients with initially diagnosed, histologically verified, non-metastatic nasopharyngeal cancer were eligible for participation in this study. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis. RESULTS: Among 274 patients, 100 (36.5%) received IMRT without replanning and 174 (63.5%) received IMRT with replanning. Five-year rates of locoregional recurrence-free survival (LRFS) were 90.1% (95%CI, 84.8% to 95.4%) and 80.8% (95%CI, 72.0% to 89.6%) for patients with and without replanning, P = 0.045. There were 17 locoregional recurrences in 15 patients among patients with replanning, of which 1 (5.9%) was out-field and 16 (94.1%) were in-field. Among patients without replanning, 19 patients developed locoregional recurrences, of which 1 (5.3%) was out-field, 2 (10.5%) were marginal, and 16 (84.2%) were in-field. CONCLUSIONS: In-field failure inside the high dose area was the most common locoregional recurrent pattern for non-metastatic NPC. Adapting the target volumes and modifying the radiation dose prescribed to the area of tumor reduction during IMRT was feasible and would not cause additional recurrence in the shrunken area.

Possible connection between intestinal tuft cells, ILC2s and obesity.

Intestinal tuft cells (TCs) are defined as chemosensory cells that can "taste" danger and induce immune responses. They play a critical role in gastrointestinal parasite invasion, inflammatory bowel diseases and high-fat diet-induced obesity. Intestinal IL-25, the unique product of TCs, is a key activator of type 2 immunity, especially to promote group 2 innate lymphoid cells (ILC2s) to secret IL-13. Then the IL-13 mainly promotes intestinal stem cell (ISCs) proliferation into TCs and goblet cells. This pathway formulates the circuit in the intestine. This paper focuses on the potential role of the intestinal TC, ILC2 and their circuit in obesity-induced intestinal damage, and discussion on further study and the potential therapeutic target in obesity.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Restoring prefrontal cortical excitation-inhibition balance with cannabidiol ameliorates neurobehavioral abnormalities in a mouse model of neurodevelopmental disorders.

Maternal immune activation (MIA) resulting from viral infections during pregnancy is linked to increased rates of neurodevelopmental disorders in offspring. However, the mechanisms underlying MIA-induced neurobehavioral abnormalities remain unclear. Here, we used a poly (I:C)-induced MIA mouse model to demonstrate the presence of multiple behavioral deficits in male offspring. Through RNA sequencing (RNA-seq), we identified significant upregulation of genes involved in axonogenesis, synaptogenesis, and glutamatergic synaptic neurotransmission in the mPFC of MIA mice. Electrophysiological analyses further revealed an excitatory-inhibitory (E/I) synaptic imbalance in mPFC pyramidal neurons, leading to hyperactivity in this brain region. Cannabidiol (CBD) effectively alleviated the behavioral abnormalities observed in MIA offspring by reducing glutamatergic transmission and enhancing GABAergic neurotransmission of mPFC pyramidal neurons. Activation of GPR55 by lipid lysophosphatidylinositol (LPI), an endogenous GPR55 agonist, specifically in the mPFC of healthy animals led to MIA-associated behavioral phenotypes, which CBD could effectively reverse. Moreover, we found that a GPR55 antagonist can mimic CBD's beneficial effects, indicating that CBD's therapeutic effects are mediated via the LPI-GPR55 signaling pathway. Therefore, we identified mPFC as a primary node of a neural network that mediates MIA-induced behavioral abnormalities in offspring. Our work provides insights into the mechanisms underlying the developmental consequences of MIA and identifies CBD as a promising therapeutic approach to alleviate these effects.