Distribution characteristics of gastric mucosal colonizing microorganisms in different glandular regions of Bactrian camels and their relationship with local mucosal immunity.

Bactrian camels inhabiting desert and semi-desert regions of China are valuable animal models for studying adaptation to desert environments and heat stress. In this study, 16S rRNA technology was employed to investigate the distribution characteristics and differences of mucosal microorganisms in the anterior gland area, posterior gland area, third gland area, cardia gland area, gastric fundic gland area and pyloric gland area of 5-peak adult healthy Bactrian camels. We aimed to explore the possible reasons for the observed microbial distribution from the aspects of histological structure and mucosal immunity. Bacteroides and Fibrobacteria accounted for 59.54% and 3.22% in the gland area, respectively, and 52.37% and 1.49% in the wrinkled stomach gland area, respectively. The gland area showed higher abundance of Bacteroides and Fibrobacteria than the wrinkled stomach gland area. Additionally, the anterior gland area, posterior gland area, third gland area, and cardia gland area of Bactrian camels mainly secreted acidic mucus, while the gastric fundic gland area mainly secreted neutral mucus and the pyloric region mainly secreted a mixture of acidic and neutral mucus. The results of immunohistochemistry techniques demonstrated that the number of IgA+ cells in the anterior glandular area, posterior glandular area, third glandular area, and cardia gland area was significantly higher than that in the fundic and pyloric gland area (p < 0.05), and the difference in IgA+ between the fundic and pyloric gland area was not significant (p > 0.05). The study revealed a large number of bacteria that can digest and degrade cellulose on the mucosa of the gastric gland area of Bactrian camels. The distribution of IgA+ cells, the structure of the mucosal tissue in the glandular region, and the composition of the mucus secreted on its surface may have a crucial influence on microbial fixation and differential distribution.

Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

Mechanisms of immune response and cell death in ischemic stroke and their regulation by natural compounds.

Ischemic stroke (IS), which is the third foremost cause of disability and death worldwide, has inflammation and cell death as its main pathological features. IS can lead to neuronal cell death and release factors such as damage-related molecular patterns, stimulating the immune system to release inflammatory mediators, thereby resulting in inflammation and exacerbating brain damage. Currently, there are a limited number of treatment methods for IS, which is a fact necessitating the discovery of new treatment targets. For this review, current research on inflammation and cell death in ischemic stroke was summarized. The complex roles and pathways of the principal immune cells (microglia, astrocyte, neutrophils, T lymphocytes, and monocytes/macrophage) in the immune system after IS in inflammation are discussed. The mechanisms of immune cell interactions and the cytokines involved in these interactions are summarized. Moreover, the cell death mechanisms (pyroptosis, apoptosis, necroptosis, PANoptosis, and ferroptosis) and pathways after IS are explored. Finally, a summary is provided of the mechanism of action of natural pharmacological active ingredients in the treatment of IS. Despite significant recent progress in research on IS, there remain many challenges that need to be overcome.

Association between variants of MTHFR genes and psychiatric disorders: A meta-analysis.

Background: Psychiatric disorders have seriously affected human life, one of the risk genes related to psychosis is the methylenetetrahydrofolatereductase (MTHFR) gene. This gene has a potential role in psychiatric disorders. Therefore, a meta-analysis is conducted to investigate the correlations between two prevalent MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T, A1298C, severe psychological disorders (schizophrenia, major depression, bipolar disorder). Methods: A total of 81 published studies were screened and selected by a search of electronic databases up to April 2022. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR polymorphism and psychiatric disorders susceptibility by using random effect models. Results: We found that MTHFR C677T polymorphism is significantly related to schizophrenia and major depression in the overall population. MTHFR C677T has been linked to an increased risk of bipolar disorder in the recessive model (TT vs. CT + CC). Ethnic subgroup analysis shows that schizophrenia and major depression significantly correlate with MTHFR C677T and A1298C in Asian populations but not Caucasians. Besides, schizophrenia is correlated substantially with MTHFR C677T in the African population. However, the MTHFR A1298C polymorphism is only marginally linked to major depression. Conclusion: Findings of the current study revealed that MTHFR may contribute to the common pathogenesis of psychiatric diseases and that its variants may be essential in controlling the expression of psychosis-related genes. This study could help the researchers and health specialists in the early diagnosis and treatment of psychiatric disorders.

Expression characteristics of polymeric immunoglobulin receptor in Bactrian camel (Camelus bactrianus) lungs.

Polymeric immunoglobulin receptor (pIgR), the transmembrane transporter of polymeric immunoglobulin A and M, has multiple immune functions. To explore the characteristics of pIgR expression in Bactrian camel lungs, twelve healthy adult (2-7 years old) Bactrian camels were systematically studied. The results showed that pIgR was mainly expressed in the cytoplasm and membrane of ciliated cells, as well as in the cytoplasm and membrane of basal cells, serous cells of bronchial glands, club cells and alveolar type 2 cells in Bactrian camel lungs. Specially, as the bronchial branches extended, the pIgR expression level in ciliated cells significantly declined (p<0.05), and the corresponding bronchial luminal areas obviously decreased (p<0.05). However, pIgR was not expressed in goblet cells, endocrine cells, alveolar type 1 cells and mucous cells of bronchial glands. The results demonstrated that ciliated cells continuously distributed throughout the whole bronchial tree mucosa were the major expression sites of pIgR, and pIgR was also expressed in basal cells, serous cells of bronchial glands, club cells and alveolar type 2 cells, which would facilitate secretory immunoglobulin A (SIgA) transmembrane transport by pIgR and form an intact protective barrier. Moreover, the pIgR expression level in ciliated cells was positively correlated with the bronchial luminal areas; but negatively correlated with the cleanliness of airflow through the bronchial cross-sections, showing that the pIgR expression level in the bronchial epithelium was inhomogeneous. Our study provided a foundation for further exploring the regulatory functions of immunoglobulins (i.e., SIgA) after transport across the membrane by pIgR in Bactrian camel lungs.

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson's Disease via Parkin.

As a typical traditional Chinese medicine, Bu-Yin-Qian-Zheng Formula (BYQZF) has been shown to have neuroprotective effects in patients with Parkinson's disease (PD), particularly by ameliorating mitochondrial dysfunction and regulating expression of the parkin protein. However, the underlying mechanisms by which BYQZF affects mitochondrial function through parkin are unclear. Accordingly, in this study, we evaluated the mechanisms by which BYQZF ameliorates mitochondrial dysfunction through parkin in PD. We constructed a parkin-knockdown cell model and performed fluorescence microscopy to observe transfected SH-SY5Y cells. Quantitative real-time reverse transcription polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of parkin. Additionally, we evaluated the cell survival rates, ATP levels, mitochondrial membrane potential (ΔΨm), mitochondrial morphology, parkin protein expression, PINK1 protein expression, and mitochondrial fusion and fission protein expression after treatment with MPP+ and BYQZF. Our results showed that cell survival rates, ATP levels, ΔΨm, mitochondrial morphology, parkin protein levels, PINK1 protein levels, and mitochondrial fusion protein levels were reduced after MPP+ treatment. In contrast, mitochondrial fission protein levels were increased after MPP+ treatment. Moreover, after transient transfection with a negative control plasmid, the above indices were significantly increased by BYQZF. However, there were no obvious differences in these indices after transient transfection with a parkin-knockdown plasmid. Our findings suggest that BYQZF has protective effects on mitochondrial function in MPP+-induced SH-SY5Y cells via parkin-dependent regulation of mitochondrial dynamics.

The distributive and structural characteristics of bronchus-associated lymphoid tissue (BALT) in Bactrian camels (Camelus bactrianus).

BACKGROUND: Bronchus-associated lymphoid tissue (BALT), distributed in the bronchial mucosa, plays a critical role in maintaining the mucosal immune homeostasis of the lower respiratory tract. The bronchial tree is a functional structure for gas exchange with the outside environment and maintains basic lung morphology. METHODS: To explore the structural and distributive characteristics of BALT in Bactrian camels, twelve healthy adult Bactrian camels were divided into two groups (six in each group). The lungs, bronchial tree and BALT were observed and analysed systematically through anatomical and histological methods. RESULTS: The results showed that Bactrian camel lungs were constituted by the left cranial lobe, left caudal lobe, right cranial lobe, right caudal lobe and accessory lobe, but lacked the middle lobe. The cranial lobe was narrow and small, the caudal lobe was extremely developed (almost four times the cranial lobe in size), and the accessory lobe was smaller than the cranial lobe; the bronchial tree, an unequal dichotomy with a tracheobronchial branch, was composed of dorsal, ventral, lateral and medial bronchiole systems. Isolated lymphoid follicles (the chief type) and aggregates of lymphoid follicles revealed two types of BALT, and germinal centres, follicle-associated epithelium and high endothelial venules could be observed in some well-developed BALT. Additionally, BALT was scattered along the bronchial tree in the entire lung, and the density increased from the trachea to the lower graded branches (densest in the bronchioles) and then decreased, with the occasional location around respiratory bronchioles or among the pulmonary mesenchyme. In the conducting portion, BALT was primarily located in the mucosa lamina propria but was also found in the submucosa, under the muscular layer, and around the submucosal glands and cartilage. CONCLUSION: The results demonstrated that the lung morphology of Bactrian camels was similar to that of horses, but the bronchial branches were more closely related to those of ruminants. These characteristics were in accordance with the morphological and structural variation regularity of lungs with species evolution. BALT was mainly scattered in the conducting portion, and bronchioles, as the final "checkpoint" in the surveillance, capture and recognition of antigens before pulmonary exchange, were the pivotal locational position of BALT. However, BALT at different depths of the bronchial wall of the conducting portion might be at different developmental stages. Our study provided evidence for further insight into the mucosal immunomodulatory mechanism of BALT in the respiratory system of Bactrian camels.

Influences of pregnancy on neuromyelitis optica spectrum disorders and multiple sclerosis.

OBJECTIVE: To assess the influences of pregnancy on disease progression of neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS). METHODS: A total of 148 NMOSD patients and 170 MS patients were reviewed retrospectively. The changes in mean annualized relapse rate (ARR) in NMOSD and MS during and after pregnancy were compared. The influences of different pregnancy outcomes on disease courses were also analyzed. RESULTS: Sixty-two relapses had occurred during pregnancy or within 1 year after delivery/abortion in NMOSD patients and 64 in MS patients. The proportion of pregnancy-related onset and relapse in NMOSD was not significantly higher than that in MS. The ARR during 0-3 months and 7-9 months postpartum/postabortal periods in NMOSD and during 0-3 months and 10-12 months postpartum/postabortal periods in MS increased significantly. The ARR in 7-9 months postpartum/postabortal period in NMOSD patients was significantly higher than that in MS patients. Different pregnancy outcomes affected the course of disease similarly in patients irrespective of NMOSD or MS. CONCLUSIONS: Both NMOSD and MS presented increased onset and relapses after delivery/abortion. Significant differences were observed in ARRs at different stages between them. Both delivery and abortion exerted detrimental effects on disease courses in NMOSD and MS.

Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission.

BACKGROUND: A prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD) is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3) and CCL13 [monocyte chemoattractant protein (MCP)-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26) and MCPs (CCL13, CCL2, CCL8, and CCL7) in patients with NMOSD during remission. METHODS: Healthy controls (HC; n = 30) and patients with MS (n = 47) and NMOSD (n = 58) in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß levels were detected using the human cytokine multiplex assay. RESULTS: Plasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1ß, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD. CONCLUSION: The study indicates that in NMOSD, the overproduction of cytokines such as IL-1ß and TNF-α during remission stimulates eosinophilic chemoattractants such as CCL13, CCL11, and CCL26, which in turn bind to their receptor (CCR3); this could lead to eosinophil hypersensitivity. These findings suggest that the elevated secretion of CCL13, CCL11, and CCL26 may be a critical step in eosinophil recruitment during NMOSD remission.

Impact of aging on distribution of IgA+ and IgG+ cells in aggregated lymphoid nodules area in abomasum of Bactrian camels (Camelus bactrianus).

The aggregated lymphoid nodules area (ALNA) in the abomasum is a special organized lymphoid tissue discovered only in Bactrian camels at present. This study aimed to explore the impact of aging on distribution of IgA+ and IgG+ cells in ALNA in abomasum of Bactrian camels. Twenty-four Alashan Bactrian camels were divided into the following four age groups: young (1-2years), pubertal (3-5years), middle-aged (6-16years) and old (17-20years). IgA+ and IgG+ cells in the lamina propria of ALNA were observed and analyzed using immunohistochemical and statistical techniques. The results showed that, in ALNA, the distribution of IgA+ and IgG+ cells were diffuse, and only a few were in subepithelium dome (SED) and most of them in non-SED. Meanwhile, there were significantly more IgA+ cells than IgG+ cells in SED from the young to the middle aged group, but which reversed in old group (P<0.05). However, the aging significantly decreased the densities of IgA+ and IgG+ cells populations in non-SED (P<0.05); in SED, there were no significant differences between the densities of IgA+ and IgG+ cells, but which were both significantly lower in old group than those in young group (P<0.05). The results demonstrated that, in mucosal effector sites, the aging significantly decreased the densities of IgA+ and IgG+ cells populations and impacted on the defense barriers formed by IgA and IgG, but had no impact on the scattered characteristics. In inductive sites, the aging dramatically declined their densities, and they should have close relationships with immune memory. These findings lay the foundation for further researching the mucosal immune disorder or decline caused by aging, and especially underscore the importance of researching the impact of aging on the relationship between IgA+ and IgG+ cells populations and the microbiota colonized in abomasum of Bactrian camels.

Glucose in human serum determined by capillary electrophoresis with glucose micro-biosensor.

A glucose micro-biosensor was employed as detector in capillary electrophoresis (CE) for determining the concentration of glucose in human serum. The micro-biosensor was based on the immobilization of the SWNTs-glucose oxidase-chitosan biocomposite at a platinized Au electrode by electrodeposition. The influencing factors including separation voltage, detection potential, pH value, and the concentration of the buffer were studied. Suitable conditions were obtained for the determination of glucose: running buffer, 25 mM PBS (pH 8.0); separation field strength, 250 V cm(-1); detection potential, 0.80 V vs. saturated calomel electrode. Under optimized detection conditions, glucose responded linearly from the range of 5 µM to 1 mM with a correlation coefficient of 0.9986 for the injection voltage of 5.0 kV and injection time of 10 s. The concentration limit of detection of the method was 1 µM (S/N = 3). The micro-biosensor exhibited good stability and durability in the analytical procedures. The relative standard deviation of the migration time and peak current were 1.7% and 2.6%, respectively. Glucose in human serum from two healthy individuals and two diabetics was successfully determined, giving a good prospect for a new clinical diagnostic instrument.