Research progress of neonatal hypoxic-ischemic encephalopathy in nonhuman primate models.

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the important complications of neonatal asphyxia, which not only leads to neurological disability but also seriously threatens the life of neonates. Over the years, animal models of HIE have been a research hotspot to find ways to cope with HIE and thereby reduce the risk of neonatal death or disability in moderate-to-severe HIE. By reviewing the literature related to HIE over the years, it was found that nonhuman primates share a high degree of homology with human gross neural anatomy. The basic data on nonhuman primates are not yet complete, so it is urgent to mine and develop new nonhuman primate model data. In recent years, the research on nonhuman primate HIE models has been gradually enriched and the content is more novel. Therefore, the purpose of this review is to further summarize the methods for establishing the nonhuman primate HIE model and to better elucidate the relevance of the nonhuman primate model to humans by observing the behavioral manifestations, neuropathology, and a series of biomarkers of HIE in primates HIE. Finally, the most popular and desirable treatments studied in nonhuman primate models in the past 5 years are summarized.

Detrended seasonal relationships and impact of climatic factors combined with spatiotemporal effect on the prevalence of human brucellosis.

Human brucellosis (HB) is a seasonal and climate-affected infectious disease that is posing an increasing threat to public health and economy. However, most of the research on the seasonal relationships and impact of climatic factors on HB did not consider the secular trend and spatiotemporal effect related to the disease. We herein utilized long-term surveillance data on HB from 2008 to 2020 using sinusoidal models to explore detrended relationships between climatic factors and HB. In addition, we assessed the impact of such climatic factors on HB using a spatial panel data model combined with the spatiotemporal effect. HB peaked around mid-May. HB was significantly correlated with climatic factors with 1-5-month lag when the respective correlations reached the maximum across the different lag periods. Each 0.1 °C increase in temperature led to 0.5% decrease in the 5-month lag incidence of HB. We also observed a positive spatiotemporal effect on the disease. Our study provides a detailed and in-depth overview of seasonal relationships and impact of climatic factors on HB. In addition, it proposes a novel approach for exploring the seasonal relationships and quantifying the impacts of climatic factors on various infectious diseases.

Current analysis of hypoxic-ischemic encephalopathy research issues and future treatment modalities.

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of long-term neurological disability in neonates and adults. Through bibliometric analysis, we analyzed the current research on HIE in various countries, institutions, and authors. At the same time, we extensively summarized the animal HIE models and modeling methods. There are various opinions on the neuroprotective treatment of HIE, and the main therapy in clinical is therapeutic hypothermia, although its efficacy remains to be investigated. Therefore, in this study, we discussed the progress of neural circuits, injured brain tissue, and neural circuits-related technologies, providing new ideas for the treatment and prognosis management of HIE with the combination of neuroendocrine and neuroprotection.

The fate and prospects of stem cell therapy in the treatment of hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of long-term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI-induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE).

Bibliometric analysis of cerebral organoids and diseases in the last 10 years.

Cerebral organoids have emerged as a powerful tool for mirroring the brain developmental processes and replicating its unique physiology. This bibliometric analysis aims to delineate the burgeoning trends in the application of cerebral organoids in disease research and offer insights for future investigations. We screened all relevant literature from the Web of Science on cerebral organoids in disease research during the period 2013-2022 and analyzed the research trends in the field using VOSviewer, CiteSpace, and Scimago Graphica software. According to the search strategy, 592 articles were screened out. The United States of America (USA) was the most productive, followed by China and Germany. The top nine institutions in terms of the number of publications include Canada and the United States, with the University of California, San Diego (USA), having the highest number of publications. The International Journal of Molecular Sciences was the most productive journal. Knoblich, Juergen A., and Lancaster, Madeline A. published the highest number of articles. Keyword cluster analysis showed that current research trends focused more on induced pluripotent stem cells to construct organoid models of cerebral diseases and the exploration of their mechanisms and therapeutic modalities. This study provides a comprehensive summary and analysis of global research trends in the field of cerebral organoids in diseases. In the past decade, the number of high-quality papers in this field has increased significantly, and cerebral organoids provide hope for simulating nervous system diseases (such as Alzheimer's disease).

Normal cerebral blood vessels under ultrasound in SD rats of different ages.

The objective of this study was to examine whether ultrasound can examine the development of cerebral vascular structure and cerebral blood flow in Sprague-Dawley (SD) rats by ultrasound in a noninvasive manner, which provides a reference for ultrasound research of SD rats. Thirty-nine SD rats (7-16 days old) were divided into seven groups according to age, and the number of SD rats in each group was, respectively, 7, 17, 1, 3, 2, 8, and 1. Ultrasound was used to detect cerebral blood vessels, cerebrovascular flow velocity, and heart rate in SD rats in the sagittal and coronal positions, and images were obtained in B-mode ultrasound. The cerebral vascular structure of 39 SD rats (7-16 days) was dynamically observed under B-ultrasound. We found that the cerebral vascular structure of the rats aged 7-10 days was clear and detectable. Rats aged 11-16 days of cerebral vascular structures became thinner and undetectable. Quantitative analysis of cerebrovascular flow rate and heart rate in rats found that there was no significant difference in cerebrovascular blood flow rate and heart rate between 7 and 8 days. Ultrasound can also be used in rat animal studies, that is, the cerebral blood flow in rats of different ages can be monitored in real-time by ultrasound in a noninvasive way.

An exploratory study on the mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of neuropathic pain.

Huangqi Guizhi Wuwu Decoction (HGWD) has a definite effect on neuropathic pain (NP), whereas the specific mechanism has not been elucidated. The components and targets in HGWD were collected and identified through System Pharmacology Database (Traditional Chinese Medicine Database and Analysis Platform). Genecards and Online Mendelian Inheritance in Man databases were used to search for NP-related genes. The Venn diagram was drawn to get the intersection target. Cytoscape 3.8.0 software was used to construct the compound-disease-target-pathway networks. STRING database was applied to analyze protein-protein interaction of potential targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were used to identify the function of genes related to NP. Finally, molecular docking was performed to visualize the binding mode and affinity between proteins and active ingredients. According to the intersection target of the Venn diagram, the network graph is constructed by Cytoscape and the results show the five compounds, ß-sitosterol, (+)-catechin, quercetin, Stigmasterol, kaempferol, and 15 genes (CASP3, FOS, GSK3B, HSP90AA1, IKBKB, IL6, MAPK8, RELA, ICAM1, SELE, ELK1, HSPB1, PRKACA, PRKCA, RAF1) were highly correlated with NP. KEGG and GO of 15 genes results that TNF, IL-17 and MAPK signaling pathway were Significantly related to the pathological mechanism of NP. Molecular docking showed that core genes in this network were IL-6 (TNF and IL-17 signaling pathways), ICAM1 (TNF signaling pathway), and CASP3 (three signal pathways). This study found that the five active compounds, three core genes, and three signaling pathways may be the key to the treatment of NP by HGWD.

Seroprevalence trend of human brucellosis and MLVA genotyping characteristics of Brucella melitensis in Shaanxi Province, China, during 2008-2020.

In this study, a total of 179,907 blood samples from populations with suspected Brucella spp. infections were collected between 2008 and 2020 and analyzed by the Rose Bengal plate test (RBPT) and serum agglutination test (SAT). Moreover, conventional biotyping, B. abortus-melitensis-ovis-suis polymerase chain reaction (AMOS-PCR), and multiple-locus variable-number tandem repeat analysis (MLVA) was applied to characterize the isolated strains. A total of 8103 (4.50%) samples were positive in RBPT, while 7705 (4.28%, 95% confidence interval (CI) 4.19-4.37) samples were positive in SAT. There was a significant difference in seroprevalence for human brucellosis over time, in different areas and different cities (districts) (χ2 = 2 = 32.23, 1984.14, and 3749.51, p < .05). The highest seropositivity (8.22% (4, 965/60393; 95% CI 8.00-8.44) was observed in Yulin City, which borders Inner Mongolia, Ningxia, and Gansu Province, China, regions that have a high incidence of human brucellosis. Moreover, 174 Brucella strains were obtained, including nine with B. melitensis bv. 1, 145 with B. melitensis bv. 3, and 20 with B. melitensis variants. After random selection, 132 B. melitensis were further genotyped using MLVA-16. The 132 strains were sorted into 100 MLVA-16 genotypes (GTs) (GT 1-100), 81 of which were single GTs represented by singular independent strains. The remaining 19 shared GTs involved 51 strains, and each GT included two to seven isolates from the Shaan northern and Guanzhong areas. These data indicated that although sporadic cases were a dominant epidemic characteristic of human brucellosis in this province, more than 38.6% (51/132) outbreaks were also found in the Shaan northern area and Guanzhong areas. The 47 shared MLVA-16 GTs were observed in strains (n = 71) from this study and strains (n = 337) from 19 other provinces of China. These data suggest that strains from the northern provinces are a potential source of human brucellosis cases in Shaanxi Province. It is urgent to strengthen the surveillance and control of the trade and transfer of infected sheep among regions.

Exploring risk transfer of human brucellosis in the context of livestock agriculture transition: A case study in Shaanxi, China.

With the booming of worldwide agriculture intensification, brucellosis, one of the most neglected zoonotic diseases, has become an increasing challenge for global public health. Although the transmission patterns of human brucellosis (HB) have been studied in many regions, the dynamic transfer processes of risk and its driving factors remain poorly understood, especially in the context of agricultural intensification. This study attempted to explore the risk transfer of HB between the exact epidemic areas and the neighboring or distant low-risk areas to explain the impact of livestock agriculture intensification and foodborne infections on the transmission of HB in Shaanxi Province as a case study. We adopted multiple approaches, including test-based methods, model-based methods, and a geographical detector to detect the spatial-temporal dynamic changes of high-risk epidemic areas of HB at the county scale. We also quantitatively estimated how the related factors drove the risk transfer of the disease. Results confirmed the risk transfer pattern of HB with an expansion from north to south in Shaanxi Province and identified two primary transfer routes. In particular, in the traditional epidemic areas of the Shaanbei plateau, the farm agglomeration effect can significantly increase the risk of HB. Meanwhile, retail outlets for milk and dairy products were partially responsible for the foodborne infections of HB in the emerging epidemic areas of Xi'an. This study not only contributed helpful insights to support HB control and prevention in the rapid transition of livestock agriculture but also provided possible directions for further research on foodborne HB infections in urbanized areas.

Changes in the epidemiological characteristics of human brucellosis in Shaanxi Province from 2008 to 2020.

In the present study, surveys of case numbers, constituent ratios, conventional biotyping, and multilocus sequence typing (MLST) were applied to characterize the incidence rate and epidemiological characteristics of human brucellosis in Shaanxi Province, China. A total of 12,215 human brucellosis cases were reported during 2008-2020, for an annual average incidence rate of 2.48/100,000. The most significant change was that the county numbers of reported cases increased from 36 in 2008 to 84 in 2020, with a geographic expansion trend from northern Shaanxi to Guanzhong, and southern Shaanxi regions; the incidence rate declined in previous epidemic northern Shaanxi regions while increasing each year in Guanzhong and southern Shaanxi regions such as Hancheng and Xianyang. The increased incidence was closely related to the development of large-scale small ruminants (goats and sheep) farms in Guanzhong and some southern Shaanxi regions. Another significant feature was that student cases (n = 261) were ranked second among all occupations, accounting for 2.14% of the total number of cases, with the majority due to drinking unsterilized goat milk. Three Brucella species were detected (B. melitensis (bv. 1, 2, 3 and variant), B. abortus bv. 3/6, and B. suis bv. 1) and were mainly distributed in the northern Shaanxi and Guanzhong regions. Three known STs (ST8, ST2, and ST14) were identified based on MLST analysis. The characteristics that had not changed were that B. melitensis strains belonging to the ST8 population were the dominant species and were observed in all nine regions during the examined periods. Strengthened human and animal brucellosis surveillance and restriction of the transfer of infected sheep (goats) as well as students avoiding drinking raw milk are suggested as optimal control strategies.

Brucellosis Outbreak Caused by Brucella melitensis - Jingyang County, Shaanxi Province, China, March-May, 2020.

What is already known about this topic? Brucellosis is one of the world's most overlooked zoonotic diseases, and humans can easily acquire brucellosis from animals and their products. Reemerging brucellosis outbreaks are probably attributable to sociocultural factors and compounded by the lack of adequate control measures in sheep and goat rearing systems. What is added by this report? This is the first identified outbreak caused by Brucella melitensisbv.3 in Jingyang County, Xianyang City, Shaanxi Province. A total of 13 seropositve cases (7 acute patients and 6 asymptomatic persons) were identified from March to May, 2020, and the investigation indicated that sheep-to-canine-to-human was the likely transmission route. What are the implications for public health practice? Effective control of sheep brucellosis will significantly reduce the risk of human brucellosis. Priority should be given to building cooperation between all stakeholders, maintaining epidemiological surveillance to detect human brucellosis at medical centers, and making case reporting mandatory for both veterinary and public health services.

Effects of acrylonitrile-induced oxidative stress on testicular apoptosis through activation of NF-κB signaling pathway in male sprague dawley rats.

Acrylonitrile (ACN) treatment can induce testicular toxicity in Sprague-Dawley (SD) rats, with the toxicity potentially related to apoptosis, mediated by nuclear factor-κB (NF-κB). The present study investigated the potential role of NF-κB in the induction of apoptosis and testicular toxicity in ACN-treated rats. Adult male SD rats were randomly divided into 3 treatment groups: a control group (corn oil), an ACN group (50 mg/kg) in which ACN was administered by gavage, and an ACN and N-acetylcysteine (ACN+NAC) group. The rats were given NAC (300 mg/kg) 30 min prior to the administration of ACN, and ACN was administered by gavage for 90 days. The ACN treatment markedly increased malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity in the testis. Glutathione (GSH) was significantly depleted in the ACN groups, and the effects of ACN were blocked by the anti-oxidant NAC. The ACN treatment also increased the expression of NF-κB (p65) and phosphorylated-IκB kinase (IKK)-α/ß and decreased the expression of an inhibitor of NF-κB (IκB-α). The pretreatment with NAC significantly inhibited the activation of NF-κB. In addition, the expression of Bax increased after the ACN treatment, and the induction of Bax was abolished by NAC. Taken together, the data suggested that ACN-induced oxidative stress activated the NF-κB signaling pathway, which modulated the expression of Bax and contributed to testicular apoptosis.

Protective effects of apigenin against acrylonitrile-induced subchronic sperm injury in rats.

This study aimed to investigate the protective effects of apigenin (AP), a flavonoid found in plants, against acrylonitrile (ACN)-induced subchronic sperm and testes injury in rats. Male Sprague-Dawley rats were randomly divided into four groups: a control group (corn oil), an ACN group (ACN 50 mg kg-1), an ACN + AP1 group (ACN + AP 234 mg kg-1), and an ACN + AP2 group (ACN + AP 468 mg kg-1). The ACN + AP group received AP by gavage after treatment with 50 mg kg-1 ACN for 30 min, whereas the rats in the control group were given an equivalent volume of corn oil. The gavage was conducted 6 days per week for 12 weeks. The results showed that AP increased the sperm concentration, motility, and mitochondrial membrane potential (MMP) (P < 0.05), which were reduced by ACN. Conversely, reactive oxygen species (ROS) and malondialdehyde (MDA) were significantly decreased by AP (P < 0.05). AP improved the damage of the ultrastructure of sperm caused by ACN. AP reduced the pathological injuries and spermatogenic cell apoptosis caused by ACN in rat testes. AP also increased glutathione peroxidase activity and decreased MDA content. In conclusion, AP reduces ACN-induced decreasing sperm quality by inhibition of inflammation and oxidative stress.