Linking phytosterols and oxyphytosterols from food to brain health: origins, effects, and underlying mechanisms.

Phytosterols and their oxidation products, namely oxyphytosterols, are natural compounds present in plant foods. With increased intake of phytosterol-enriched functional food products, the exposure of both phytosterols and oxyphytosterols is rising. Over the past ten years, researches have been focused on their absorption and metabolism in human body, as well as their biological effects. More importantly, recent studies showed that phytosterols and oxyphytosterols can traverse the blood-brain barrier and accumulate in the brain. As brain health problems resulting from ageing being more serious, attenuating central nervous system (CNS) disorders with active compounds in food are becoming a hot topic. Phytosterols and oxyphytosterols have been shown to implicated in cognition altering and the pathologies of several CNS disorders, including Alzheimer's disease and multiple sclerosis. We will overview these findings with a focus on the contents of phytosterols and oxyphytosterols in food and their dietary intake, as well as their origins in the brain, and illustrate molecular pathways through which they affect brain health, in terms of inflammation, cholesterol homeostasis, oxidative stress, and mitochondria function. The existing scientific gaps of phytosterols and oxyphytosterols to brain health in knowledge are also discussed, highlighting research directions in the future.

Early Toll-like receptor 4 inhibition improves immune dysfunction in the hippocampus after hypoxic-ischemic brain damage.

Background: Toll-like receptor 4 (TLR4) is implicated in neonatal hypoxic-ischemic brain damage (HIBD), but the underlying mechanism is unclear. Hypothesis: We hypothesized that TLR4 mediates brain damage after hypoxic ischemia (HI) by inducing abnormal neuroimmune responses, including activation of immune cells and expression disorder of immune factors, while early inhibition of TLR4 can alleviate the neuroimmune dysfunction. Method: Postnatal day 7 rats were randomized into control, HI, and HI+TAK-242 (TAK-242) groups. The HIBD model was developed using the Rice-Vannucci method (the left side was the ipsilateral side of HI). TAK-242 (0.5 mg/kg) was given to rat pups in the TAK-242 group at 30 min before modeling. Immunofluorescence, immunohistochemistry, and western blotting were used to determine the TLR4 expression; the number of Iba-1+, GFAP+, CD161+, MPO+, and CD3+ cells; ICAM-1 and C3a expression; and interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-10 expression in the hippocampal CA1 region. Result: Significantly increased TLR4 expression was observed in the left hippocampus, and was alleviated by TAK-242. The significant increases in Iba-1+, MPO+, and CD161+ cells at 24 h and 7 days after HI and in GFAP+ and CD3+ T cells at 7 days after HI were also counteracted by TAK-242, but no significant differences were observed among groups at 24 h after HI. ICAM-1 expression increased 24 h after HI, while C3a expression decreased; TAK-242 also alleviated these changes. TNF-α and IL-1ß expression increased, while IL-10 expression decreased at 24 h and 7 days after HI; TAK-242 counteracted the increased TNF-α and IL-1ß expression at 24 h and the changes in IL-1ß and IL-10 at 7 days, but induced no significant differences in IL-10 expression at 24 h and TNF-α expression at 7 days. Conclusion: Early TLR4 inhibition can alleviate hippocampal immune dysfunction after neonatal HIBD.

Dietary cholesterol oxidation products: Perspectives linking food processing and storage with health implications.

Dietary cholesterol oxidation products (COPs) are heterogeneous compounds formed during the processing and storage of cholesterol-rich foods, such as seafood, meat, eggs, and dairy products. With the increased intake of COPs-rich foods, the concern about health implications of dietary COPs is rising. Dietary COPs may exert deleterious effects on human health to induce several inflammatory diseases including atherosclerosis, neurodegenerative diseases, and inflammatory bowel diseases. Thus, knowledge regarding the effects of processing and storage conditions leading to formation of COPs is needed to reduce the levels of COPs in foods. Efficient methodologies to determine COPs in foods are also essential. More importantly, the biological roles of dietary COPs in human health and effects of phytochemicals on dietary COPs-induced diseases need to be established. This review summarizes the recent information on dietary COPs including their formation in foods during their processing and storage, analytical methods of determination of COPs, metabolic fate, implications for human health, and beneficial interventions by phytochemicals. The formation of COPs is largely dependent on the heating temperature, storage time, and food matrices. Alteration of food processing and storage conditions is one of the potent strategies to restrict hazardous dietary COPs from forming, including maintaining relatively low temperatures, shorter processing or storage time, and the appropriate addition of antioxidants. Once absorbed into the circulation, dietary COPs can contribute to the progression of several inflammatory diseases, where the absorbed dietary COPs may induce inflammation, apoptosis, and autophagy in cells in the target organs or tissues. Improved intake of phytochemicals may be an effective strategy to reduce the hazardous effects of dietary COPs.

PDCD1 strengthens the sensitivity of ovarian cancer to cisplatin chemotherapy by promoting apoptosis.

PURPOSE: The primary purpose of this study was to make clear the role of PDCD1 in the occurrence and progression of ovarian cancer, and explain its mechanism. METHODS: RT-PCR, westem blot, MTT and immunohistochemistry were used to detect the expression levels of PDCD1 mRNA and protein in human ovarian cancer cell lines (SKOV3, 3AO, CAOV3 and OVCAR3), human normal ovary, serous cystadenoma, and serous cystadenocarcinoma tissue. SKOV3, SKOV3-MOCK, and SKOV3-PDCD1 cells were subcutaneously injected into the armpit of nude mice to observe the effect of PDCD1 expression on tumorigenic ability. Cisplatin, carboplatin, cyclophosphamide, etoposide and paclitaxel were used in the experiments. RESULTS: PDCD1 was lowly expressed in SKOV3 and 3AO, moderately expressed in CAOV3, and highly expressed in OVCAR3. PDCD1 significantly inhibited the proliferation and clone formation ability of the ovarian carcinoma cell line SKOV3. In the SKOV3-PDCD1 group, the tumor formation rate decreased significantly and the tumor formation time prolonged significantly. The CAOV3 and OVCAR3 cells with high expression of PDCD1 were more sensitive to cisplatin. The SKOV3 and 3AO cells with low expression of PDCD1 were less sensitive to cisplatin. Compared with the SKOV3- MOCK control group, the apoptosis rate and the expression levels of the caspase-3/8 proteins activity increased significantly in the PDCD1 overexpression group. The expression levels of caspase-9 and Bax increased slightly. No significant changes were observed in the expression of Bcl-2. CONCLUSION: The expression of PDCD1 decreased significantly in human ovarian cancer. Overexpression of PDCD1 can inhibit the proliferation capacity of ovarian cancer. PDCD1 strengthens the sensitivity of ovarian cancer to cisplatin by promoting cisplatin-induced apoptosis.

Carpets with visual cues can improve gait in Parkinson's disease patients: may be independent of executive function.

BACKGROUND: Gait impairment is common in Parkinson's disease (PD) patients, which greatly reduces their quality of life. Executive dysfunction is associated with gait impairment. Compensatory strategies, including visual cues, have been shown to be effective in improving PD gait. In this study, we aimed to understand whether carpets with visual cues could improve PD gait, and how the improvement varies across patients with different executive function state. METHODS: We designed carpets with chessboard and stripe cues. A total of 65 Chinese PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, L-dopa equivalent daily dosage, Hoehn & Yahr stage, Frontal Assessment Battery, Mini Mental State Examination Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were evaluated. Gait parameters including stride length, gait speed and fall risk were recorded by a wearable electronic device. RESULTS: The stride length and gait speed were significantly improved and the fall risk was significantly mitigated when PD patients walked on carpets with chessboard and stripe patterns. Further analysis showed the amelioration of gait parameters was independent of executive dysfunction. CONCLUSIONS: Our study demonstrates that carpets with visual cues can improve the gait of PD patients even in those with mild executive dysfunction.

Stigmasterol attenuates inflammatory response of microglia via NF-κB and NLRP3 signaling by AMPK activation.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Although its pathogenesis remains unclear, studies have indicated microglia-mediated neuroinflammation playing an important role. Phytosterols are a class of natural compounds presented in food, and have anti-inflammatory abilities. Recent studies suggested that phytosterols can traverse the blood-brain barrier and enter the brain, however, it remains largely unknown that whether phytosterols affect neuroinflammation in the AD pathogenesis. Here, we used APPswe/PS1dE9 mice as the animal model of AD, and found that stigmasterol treatment attenuated cognitive deficits, and decreased Aß42 concentration in cortex and hippocampus. Stigmasterol treatment also suppressed neuroinflammation, by reducing pro-inflammatory cytokine levels and microglia activation. Next, we simulated BV2 cells with Aß42 oligomers, which induced inflammatory responses of microglia. Stigmasterol protected BV2 cells against Aß42 oligomers induced inflammation, and mediated secretion of pro-inflammatory cytokines via NF-κB and NLRP3 signaling pathways by AMPK activation. Stigmasterol also alleviated the M1 polarization of BV2 cells. In general, our study demonstrates that stigmasterol ameliorated neuroinflammation in APP/PS1 mice, and suppressed inflammatory response of microglia to Aß42 oligomers via AMPK/NF-κB and AMPK/NLRP3 signaling, which provides a mechanistic insight for stigmasterol in anti-inflammation and AD therapy.

Preoperative nutritional evaluation of prostate cancer patients undergoing laparoscopic radical prostatectomy.

BACKGROUND AND OBJECTIVE: Prostate cancer (PCa) is one of the most common malignant tumors in men. Geriatric Nutritional Risk Index (GNRI) is an objective index for evaluating nutritional status of elderly people over 65 years old. The aim of the current study was to explore the correlation and predictive value between GNRI and postoperative recovery and complications in PCa patients undergoing laparoscopic radical prostatectomy (LRP). METHODS: Taking 98 as the GNRI boundary value, 96 PCa patients (aged≥65 y) undergoing LRP in the Department of Urology, Affiliated Hospital of North Sichuan Medical College from January 2018 to December 2020 were grouped into malnutrition group (MNg, 34 patients, 35.4%) and normal nutrition group (NNg, 62 patients, 64.6%). Basic information, laboratory examination indexes, operation conditions, postoperative complications and postoperative recovery indexes of patients were recorded and retrospectively analyzed. Clavien-Dindo Classification System (CDCS) was used to assess postoperative complications. T-test was used to analyze differences between the two groups. ROC curve was generated to determine the predictive value of GNRI for postoperative complications. RESULTS: Percentage of complications was significantly higher in MNg group compared with that in NNg group (P < 0.01). The average grade based on CDCS was significantly lower in NNg group compared with that in MNg group (P < 0.01). Body weight, Body Mass Index (BMI), preoperative hemoglobin value (HGB), serum albumin (ALB) values of MNg and NNg were significantly positively correlated with GNRI (P<0.01). Incidence and severity of postoperative complications of MNg patients were significantly higher compared with those of NNg patients (P<0.05). Average hospitalization cost of MNg patients was higher in MNg patients compared with that of NNg patients (P<0.05). Duration of post-anesthesia care unit (PACU), duration of antibiotic use and duration of indwelling drainage tube were longer in MNg patients compared with those in NNg patients (P<0.05). Furthermore, volume of indwelling drainage tube was higher in MNg patients compared with that in NNg patients (P<0.05). CONCLUSION: GNRI is an effective and reliable tool for evaluation of preoperative nutritional status of prostate cancer patients. The findings showed that GNRI is correlated with postoperative recovery and complications, and is an effective predictive marker.

Parkinsonism-Hyperpyrexia Syndrome and Dyskinesia-Hyperpyrexia Syndrome in Parkinson's Disease: Two Cases and Literature Review.

Parkinsonism-hyperpyrexia syndrome (PHS) and dyskinesia-hyperpyrexia syndrome (DHS) are rare but exhibit life-threatening complications in Parkinson's disease (PD). We herein presented two cases of PD patients and performed a comprehensive and comparative literature review for these two syndromes. The first case was diagnosed as PHS with cerebral salt wasting syndrome caused by abrupt withdrawal of antiparkinsonian medication. Her symptoms were gradually remitted with reinstitution of the medication. The second one was an early-stage PD patient diagnosed as DHS in association with abuse of antiparkinsonian drugs. Her symptoms were gradually remitted with reduced dosage of dopaminergic drugs. Results of literature reviews revealed a total of 56 and 13 cases of PHS and DHS, respectively, and they were more likely to occur in elderly and long-term PD patients. These two syndromes showed different female-to-male ratio, similar mortality, and different recovery time. There were stark differences between PHS and DHS, including triggers (abrupt drug stoppage versus drug abuse), symptoms (worsened tremor and rigidity versus continuous dyskinesia), and treatment (drug reinstitution versus drug reduction). In summary, our reports and the review provide new insights into PHS and DHS in association with PD and may facilitate rapid discrimination of the syndromes for timely and proper treatment to reduce mortality.

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.

Toll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. L. reuteri treatment was carried out in vivo and vitro study. Compared with wild-type mice, AP and AP-associated gut injury were exacerbated in TLR4ΔIEC mice in a gut microbiota-dependent manner. The relative abundance of Lactobacillus and number of Paneth cells remarkably decreased in TLR4ΔIEC mice. The KEGG pathway analysis derived from RNA sequencing suggested that genes affected by intestinal TLR4 deletion were related to the activation of nod-like receptor pathway. Furthermore, L. reuteri treatment could significantly improve the pancreatic and intestinal injury in TLR4ΔIEC mice through promoting Paneth cells in a NOD2-dependent manner. Loss of intestinal epithelial TLR4 exacerbated pancreatic and intestinal damage during AP, which might be attributed to the gut microbiota dysbiosis especially the exhausted Lactobacillus. L. reuteri might maintain intestinal homeostasis and alleviate AP via Paneth cells modulation.Abbreviations: AP Acute pancreatitis, TLR4 Toll-like receptor 4, IL-1ß Interleukin-1ß, IL-6 Interleukin-6, TNF-α Tumor necrosis factor-α, SIRS Systematic inflammatory response syndrome, LPS Lipopolysaccharides, SPF Specific pathogen-free, ZO-1 Zonula occludens-1, CON Control, H&E Hematoxylin and eosin, FISH Fluorescence in situ hybridization, DAPI 4',6-diamidino-2-phenylindole, PCoA Principal co-ordinates analysis, SCFA Short chain fatty acid, LEfSe Linear discriminant analysis Effect Size, ANOVA Analysis of variance, F/B Firmicutes/Bacteroidetes, PCA Principal component analysis, NOD2 Nod-like receptor 2, ABX antibiotics, PCNA proliferating cell nuclear antigen.

Neck pain and absence of cranial nerve symptom are clues of cervical myelopathy mimicking stroke: Two case reports.

BACKGROUND: Cervical myelopathy is a potential stroke imitator, for which intravenous thrombolysis would be catastrophic. CASE SUMMARY: We herein present two cases of cervical myelopathy. The first patient presented with acute onset of right hemiparesis and urinary incontinence, and the second patient presented with sudden-onset right leg monoplegia. The initial diagnoses for both of them were ischemic stroke. However, both of them lacked cranial nerve symptom and suffered neck pain at the beginning of onset. Their cervical spinal cord lesions were finally confirmed by cervical computed tomography. A literature review showed that neck pain and absence of cranial nerve symptom are clues of cervical myelopathy. CONCLUSION: The current report and the review remind us to pay more attention to these two clues in suspected stroke patients, especially those within the thrombolytic time window.

Methodological framework for identifying sustainability intervention priority areas on coastal landscapes and its application in China.

In regional sustainability evaluation and policy analysis, the paradigm of safe operating spaces (SOS) has been widely applied. Yet, SOS is not readily useful for informing policy interventions toward sustainability transition. This study reports on a methodological framework that operationalizes SOS at the regional scale for designing spatially targeted sustainability interventions. In particular, this framework accounts for teleology by integrating policy orientations of the place-variant "major function" of development, and provides early-warnings by integrating long-term social-environmental trends. The framework we proposed has been applied by the Chinese government in a coastal province (Liaoning) for a landscape sustainability project, which is introduced here step-by-step. The four main steps include: (1) Quantifying SOS status across multiple "what to sustain" dimensions, e.g., land scarcity, water scarcity, pollutant discharge, and ecosystem health for the inland, and coastal exploitation intensity, marine environmental quality, and marine ecosystem biodiversity for the sea. (2) Quantifying SOS status in terms of the place-variant "what to develop" dimensions, e.g., urbanization-oriented, agriculture-stock-oriented, versus conservation-oriented development. (3) Integrating the two as a composite indicator of three ordinal levels to classify the current SOS status. (4) Developing a multi-level sustainability early-warning system by cross-analysis of the SOS status and social-environmental interaction trends (e.g., changes in, e.g., resource utilization efficiency, pollutant discharge, and eco-environmental quality). The potential use of the framework is demonstrated through the case of Liaoning Province, China, which helps policy-makers to identify priority areas for sustainability interventions. Methodological robustness and future directions of applying this multi-level sustainability early-warning system are further discussed.

Tuber flours improve intestinal health and modulate gut microbiota composition.

The different health effects between starch and whole flour from tubers are rarely studied. Here, we investigated the effects of cassava flour (CF), cassava starch (CS), potato flour (PF), and potato starch (PS) on gut health and gut microbiota of normal rats. Feed analysis showed that CF and PF diet provided significantly more slowly digestible and resistant starch, less rapidly digestible starch. Compared with rats fed with PS and CS diets, rats fed with PF and CF diets gained less body weight and have tighter intestinal barrier. Butyric acid contents were increased by tuber flours. CF and PF selectively promoted the relative abundance of Akkermansia and Eubacterium ruminantium in cecal and colonic content. In conclusion, tuber flour has intestinal protection, body weight control, and gut microbiota improving ability compared with starch. The different composition of starch might be the basis for these effects.

Sterols and Sterol Oxidation Products: Effect of Dietary Intake on Tissue Distribution in ApoE-Deficient Mice.

Sterols and sterol oxidation products (SOPs) are well-known dietary factors influencing atherosclerosis; however, their distribution in vivo after dietary sterol/SOP intake is still unclear. Here, we investigated the tissue distribution of sterols and SOPs in ApoE-/- mice after dietary exposure to diets supplemented with phytosterols (PS), phytosterol oxidation products (POPs), or cholesterol oxidation products (COPs). The results showed that PS intake reduced cholesterol in serum and the liver but increased cholesterol in the brain. PS intake increased the levels of PS in vivo and the levels of 7-keto- and triol-POPs in serum and the liver. COP intake elevated the level of all COPs in serum but did not change the 7-keto-cholesterol level in the liver and brain. All POPs in serum and parts of POPs in the liver and brain increased after dietary POP exposure. Our study indicated that dietary PS and SOPs accumulated in vivo with varying degrees and influenced cerebral cholesterol metabolism.

Automated whole breast segmentation for hand-held ultrasound with position information: Application to breast density estimation.

BACKGROUND AND OBJECTIVE: Women with higher breast densities have a relatively higher risk to be diagnosed with breast cancer. Hand-held ultrasound (HHUS) can provide precise screening results and detect masses in dense breasts. However, its lack of position information and automatic extraction of breast area hinder the implementation of density estimation. To facilitate reliable breast density evaluation, this study proposed an upgraded version of our whole-breast ultrasound (WBUS) system, which not only can provide precise position information, but also can extract precise breast area automatically based on deep learning method. METHODS: WBUS images with probe position information were collected from 117 women. For each case, an automatic breast region segmentation by DeepResUnet was conducted, then fibroglandular tissues were extracted from breast region using fuzzy c-mean (FCM) classifier. Finally, the percentage of breast density and breast area of the DeepResUnet predicted region and the breast region of the ground truth were calculated and compared. RESULTS: The average and standard deviation of each breast case for DeepResUnet predicted breast region of 10-fold in Accuracy (ACC) was 0.963±0.054. Sensitivity (SENS) was 0.928±0.11. Specificity (SPEC) was 0.967±0.054. Dice coefficient (Dice) was 0.916±0.98. Region intersection over union (IoU) was 0.856±0.134. Significant and very high correlations of breast density, fibroglandular tissue area and breast area (R = 0.843, R= 0.822 and R = 0.984, all p values < 0.001) were found between the ground truth and the result of the proposed method for ultrasound images. CONCLUSIONS: Breast density, fibroglandular tissue, and breast volume evaluated based on the proposed method and WBUS system have significant correlations with ground truth, indicating that the proposed method and WBUS system has the potential to be an alternative modality for breast screening and density estimation in clinical use.

Discovery of Keap1-Nrf2 small-molecule inhibitors from phytochemicals based on molecular docking.

Various phytochemicals have been reported to protect against oxidative stress. However, the mechanism underlying has not been systematically evaluated, which limited their application in disease treatment. Nuclear factor erythroid 2-related factor 2 (Nrf2), a central transcription factor in oxidative stress response related to numerous diseases, is activated after dissociating from the cytoskeleton-anchored Kelch-like ECH-associated protein 1 (Keap1). The Keap1-Nrf2 protein-protein interaction has become an important drug target. This study was designed to clarify whether antioxidantive phytochemicals inhibit the Keap1-Nrf2 protein-protein interaction and activate the Nrf2-ARE signaling pathway efficiently. Molecular docking and 3D-QSAR were applied to evaluate the interaction effects between 178 antioxidant phytochemicals and the Nrf2 binding site in Keap1. The Nrf2 activation effect was tested on a H2O2-induced oxidative-injured cell model. Results showed that the 178 phytochemicals could be divided into high-, medium-, and low-total-score groups depending on their binding affinity with Keap1, and the high-total-score group consisted of 24 compounds with abundant oxygen or glycosides. Meanwhile, these compounds could bind with key amino acids in the structure of the Keap1-Nrf2 interface. Compounds from high-total-score group show effective activation effects on Nrf2. In conclusion, phytochemicals showed high binding affinity with Keap1 are promising new Nrf2 activators.

A Novel Modified Hydrated Sodium Calcium Aluminosilicate (HSCAS) Adsorbent Can Effectively Reduce T-2 Toxin-Induced Toxicity in Growth Performance, Nutrient Digestibility, Serum Biochemistry, and Small Intestinal Morphology in Chicks.

The objective of this study was to evaluate the ability of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce the toxicity of T-2 toxin in broilers. Ninety-six one-day-old male broilers were randomly allocated into four experimental groups with four replicates of six birds each. The four groups, 1-4, received a basal diet (BD), a BD plus 6.0 mg/kg T-2 toxin, a BD plus 6.0 mg/kg T-2 toxin with 0.05% modified HSCAS adsorbent, and a BD plus 0.05% modified HSCAS adsorbent, respectively, for two weeks. Growth performance, nutrient digestibility, serum biochemistry, and small intestinal histopathology were analyzed. Compared to the control group, dietary supplementation of T-2 toxin decreased (p < 0.05) body weight gain, feed intake, and the feed conversion ratio by 11.4%-31.8% during the whole experiment. It also decreased (p < 0.05) the apparent metabolic rates of crude protein, calcium, and total phosphorus by 14.9%-16.1%. The alterations induced by T-2 toxin were mitigated (p < 0.05) by the supplementation of the modified HSCAS adsorbent. Meanwhile, dietary modified HSCAS adsorbent supplementation prevented (p < 0.05) increased serum aspartate aminotransferase by T-2 toxin at d 14. It also prevented (p < 0.05) T-2 toxin-induced morphological changes and damage in the duodenum, jejunum, and ileum of broilers. However, dietary supplementation of the modified HSCAS adsorbent alone did not affect (p > 0.05) any of these variables. In conclusion, these findings indicate that the modified HSCAS adsorbent could be used against T-2 toxin-induced toxicity in growth performance, nutrient digestibility, and hepatic and small intestinal injuries in chicks.

The response of glandular gastric transcriptome to T-2 toxin in chicks.

This study was conducted to determine the effect of T-2 toxin on the transcriptome of the glandular stomach in chicks using RNA-sequencing (RNA-Seq). Four groups of 1-day-old Cobb male broilers (n = 4 cages/group, 6 chicks/cage) were fed a corn-soybean-based diet (control) and control supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. The histological results showed that dietary supplementation of T-2 toxin at 3.0 and 6.0 mg/kg induced glandular gastric injury including serious inflammation, increased inflammatory cells, mucosal edema, and necrosis and desquamation of the epithelial cells in the glandular stomach of chicks. RNA-Seq analysis revealed that there were 671, 1393, and 1394 genes displayed ≥2 (P < 0.05) differential expression in the dietary supplemental T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, compared with the control group. Notably, 204 differently expressed genes had shared similar changes among these three doses of T-2 toxin. GO and KEGG pathway analysis results showed that many genes involved in oxidation-reduction process, inflammation, wound healing/bleeding, and apoptosis/carcinogenesis were affected by T-2 toxin exposure. In conclusion, this study systematically elucidated toxic mechanisms of T-2 toxin on the glandular stomach, which might provide novel ideas to prevent adverse effects of T-2 toxin in chicks.

Use of free peritoneal and bladder mucosal grafts as ureteral mucosa substitutes for management of avulsion of the ureteral mucosa in a dog model.

BACKGROUND AND PURPOSE: Avulsion of the ureteral mucosa is one of the most serious complications of ureteroscopy and considered challenging for urologic surgeons. In this study, we developed two novel methods to reconstruct the impaired ureter. MATERIALS AND METHODS: After ureteral mucosal avulsion in a canine model, ureteral reconstruction was performed in one of three ways: free tabularized peritoneal grafts (group A, n = 6); bladder mucosal grafts (group B, n = 6); or simple stenting technique (control group [n = 3]). At postoperative week 10, evaluation with intravenous urography (IVU) was followed by harvesting of reconstructed ureter segments for pathologic analysis. RESULTS: IVU showed nonvisualization of the collecting system of the affected side and histologic evaluation showed imperforation or stenosis in all animals in the control group. IVU showed good visualization of the reconstructed ureter without stenosis in group A and in most animals in group B. There was a mild dilation but no obvious stenosis in one animal in group B. Microscopically, all the reconstructed ureteral lumens were uniformly lined with transitional epithelium. Extensive neovascularity was evident in the subepithelial layer with a streaming of fibroblasts toward the neomucosa. CONCLUSION: Replacing the avulsed mucosa in the injured ureter with tubularized peritoneal free grafts or bladder mucosal grafts may be an optimal method to manage avulsion of the ureteral mucosa.

Dawn of Advanced Thyroid Cancer Therapy: Targeted Therapy and Immunotherapy / 肿瘤防治研究

In recent years, the incidence of thyroid cancer has increased significantly. Most of the cases are differentiated thyroid cancer, which is characterized by a good prognosis. However, 15% of patients still have persistent or recurrent disease after initial treatment, and those with locally advanced or metastatic cancer are not cured with established treatments and at risk of death. The treatment of advanced thyroid cancer is still controversial at home and abroad, but it tends to targeted therapy and immunotherapy. With the in-depth understanding of the molecular pathogenesis of thyroid cancer, a variety of new targeted therapies have been approved for advanced thyroid cancer. The 2021 guidelines of the Chinese Society of Clinical Oncology (CSCO) and the 2022 guidelines of the European Society of Oncology (ESMO) regard targeted therapy as a level I recommendation for the treatment of advanced thyroid cancer. This article reviews the new progress in clinical treatment of advanced thyroid carcinoma.

Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases.

The amygdala is an almond-shaped nucleus located deep and medially within the temporal lobe and is thought to play a crucial role in the regulation of emotional processes. GABAergic neurotransmission inhibits the amygdala and prevents us from generating inappropriate emotional and behavioral responses. Stress may cause the reduction of the GABAergic interneuronal network and the development of neuropsychological diseases. In this review, we summarize the recent evidence investigating the possible mechanisms underlying GABAergic control of the amygdala and its interaction with acute and chronic stress. Taken together, this study may contribute to future progress in finding new approaches to reverse the attenuation of GABAergic neurotransmission induced by stress in the amygdala.