Tenuifolin improves learning and memory by regulating long-term potentiation and dendritic structure of hippocampal CA1 area in healthy female mice but not male mice.

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.

Multiple brain regions are involved in reaction to acute restraint stress in CYLD-knockout mice.

The lysine 63 deubiquitinase cylindromatosis (CYLD) is expressed at high levels in the brain and is considered to be involved in anxious and depressive behavior, cognitive inflexibility, and autism disorders. Previous research was limited in some brain regions, including the hippocampus, striatum, and amygdala. To better understand whether CYLD plays a role in adaptation to stress and which brain regions are involved, we analyzed the behavior of CYLD-knockout mice in the elevated plus maze (EPM) and light-dark box test (LDT) after acute restraint stress (ARS) and mapped their c-Fos immunoreactivity in brain sections. Here we report that CYLD deficiency leads to an unexpected reaction to ARS in mice, and is accompanied by significant neuronal activation of brain regions including the medial prefrontal cortex (mPFC), dorsal striatum (DS), nucleus accumbens (NAc), and basal lateral amygdala (BLA), but not ventral hippocampus (vHPC). Our findings show that CYLD participates in ARS-induced anxious behavior and that this involves multiple brain regions.

Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation.

Introduction: Vaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing. Methods: Vaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities. Results: The microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study. Conclusion: These findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.

[Risk Factors of Rapidly Progressive Interstitial Lung Disease in Patients With Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis].

Objective: To investigate the conditions of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis combined with rapidly progressive interstitial lung disease (RPILD), and to analyze the risk factors. Methods: A total of 145 patients diagnosed with anti-MDA5 antibody-positive dermatomyositis at West China Hospital, Sichuan University between January 2018 and September 2021 were selected, and their general and clinical data were collected. The patients were divided into two groups, a RPILD group of patients with comorbid RPILD and a non-RPILD group of those who did not have comorbid RPILD. Factors that might affect whether patients with anti-MDA5 antibody-positive dermatomyositis also had comorbid RPILD were screened out and binary logistic regression analysis was performed. Results: Among the 145 patients with anti-MDA5 antibody-positive dermatomyositis, 32 (22.07%) patients had comorbid RPILD, while the remaining 113 (77.93%) did not have comorbid RPILD. Binary logistic regression analysis showed that lactate dehydrogenase≥370 IU/L (compared with <370 IU/L, OR=4.066, 95% CI: 1.616-10.230) and carcinoembryo antigen≥5 ng/mL (compared with <5 ng/mL, OR=6.070, 95% CI: 2.013-18.303) were risk factors for comorbid RPILD in patients with anti-MDA5 antibody-positive dermatomyositis ( ß>0, OR>1, P<0.05). Conclusion: It is recommended that close attention be given to changes in high-resolution chest CT and pulmonary functions in patients with lactate dehydrogenase≥370 IU/L and carcinoembryo antigen≥5 ng/mL. If rapid progression of lung disease is detected, it is necessary to strengthen the treatment of the lung disease, thereby improving the prognosis of patients.

Cordycepin improved the cognitive function through regulating adenosine A2A receptors in MPTP induced Parkinson's disease mice model.

BACKGROUND: Parkinson's disease (PD), the most common neurodegenerative disorder, primarily affects dopaminergic neurons in the substantia nigra (SN). In addition to severe motor dysfunction, PD patients appear apparent cognitive impairments in the late stage. Cognitive dysfunction is accompanied by synaptic transmission damage in the hippocampus. Cordycepin has been reported to alleviate cognitive impairments in neurodegenerative diseases. PURPOSE: The study aimed to estimate the protection roles of cordycepin on cognitive dysfunction in PD model and explore the potential mechanisms. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the PD model in vivo and in vitro experiments. In the in vivo experiments, the C57BL / 6 mice were intraperitoneally injected with MPTP and intragastric administration with cordycepin. Open field test (OFT) was used to estimate the exercise ability. Spontaneous alternation behavioral (SAB) and morris water maze (MWM) tests were used to evaluate the learning and memory abilities. The hippocampal slices from C57BL / 6 and Kunming mice in the in vitro experiments were used to record field excitatory postsynaptic potential (fEPSP) by electrophysiological methods. Western blotting was used to examine the level of tyrosine hydroxylase (TH) in the in vivo experiments and the levels of adenosine A1 and A2A receptors (A1R and A2AR) in the in vitro experiments, respectively. The drugs of MPTP, cordycepin, DPCPX and SCH58261 were perfused through dissolving in artificial cerebrospinal fluid. RESULTS: Cordycepin could significantly reduce the impairments on motor, exploration, spatial learning and memory induce by MPTP. MPTP reduced the amplitude of LTP in hippocampal CA1 area but cordycepin could improve LTP amplitudes. Cordycepin at dosage of 20 mg/kg also increased the TH level in SN. In the in vitro experiments, MPTP inhibited synaptic transmission in hippocampal Schaffer-CA1 pathway with a dose-dependent relationship, while cordycepin could reverse the inhibition of synaptic transmission. Furthermore, the roles of cordycepin on synaptic transmission could been attenuated in the presence of the antagonists of A1R and A2AR, DPCPX and SCH58261, respectively. Interestingly, the level of A2AR rather than A1R in hippocampus was significantly decreased in the cordycepin group as compared to the control. CONCLUSION: The present study has showed that cordycepin could improve cognitive function in the PD model induced by MPTP through regulating the adenosine A2A receptors. These findings were helpful to provide a new strategy for the dementia caused by Parkinson's disease.

Mefunidone ameliorates lipopolysaccharide-induced acute lung injury through inhibiting MAPK signaling pathway and enhancing Nrf2 pathway.

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms. METHODS: We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs). RESULTS: MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes. CONCLUSION: Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.

The rare genera Picacharops Gauld and Sliochia Gauld (Hymenoptera, Ichneumonidae, Campopleginae) found in China, with description of two new species.

Two rare genera are newly reported for China: the Australasian Picacharops Gauld, 1984 and the Oriental Sliochia Gauld, 1976. A new species of these two monotypic genera (P. granulosus sp. nov. and S. adustifemur sp. nov., respectively) is described from China and illustrated. Keys to species of both genera are also provided.

Review of the genera Breviterebra Kusigemati, Charops Holmgren and Scenocharops Uchida (Hymenoptera, Ichneumonidae, Campopleginae) from China, with description of three new species.

Species of the genera Breviterebra Kusigemati, 1982, Charops Holmgren, 1859 and Scenocharops Uchida, 1932 (Hymenoptera, Ichneumonidae, Campopleginae) from China are revised. Of the 13 species recognized, three are described as new species: Breviterebra apicocrinis sp. nov., Charops mauroknemus sp. nov. and Scenocharops yunnanensis sp. nov. The genus Breviterebra Kusigemati and the species Scenocharps montanus Gupta Maheshwary, 1971 are recorded in China for the first time. The distribution area of C. brachypterus (Cameron), C. striatus (Uchida), S. flavipetiolus (Sonan) and S. parasae He in China are updated. DNA barcode fragment of the mitochondrial COI gene of B. apicocrinis sp. nov. is presented. Keys to Breviterebra, Charops and Scenocharops are provided.

Four rare genera of the subfamily Campopleginae (Hymenoptera: Ichneumonidae) from China, with description of three new species.

Five species of four rare genera Dolophron Förster, 1869, Genotropis Townes, 1970, Leptocampoplex Horstman, 1970 and Philositus Townes, 1970 of the family Ichneumonidae (Hymenoptera) are found in China, among which three genera Dolophron, Leptocampoplex and Philositus are firstly reported from China. Three new species D. granulosa sp. nov., G. mauroknema sp. nov., and P. parva sp. nov. are described and illustrated. Redescriptions of Genotropis clara Townes, 1970 and Leptocampoplex cremastoides (Holmgren, 1860) are given. Keys to species of each genus and the distribution map of China are also provided.

Five new species of the genus Sinophorus Frster (Hymenoptera, Ichneumonidae, Campopleginae) from China.

Five new species of the genus Sinophorus Frster, 1869 (Ichneumonidae, Campopleginae) are described and illustrated from China: S. dioryctriae sp. nov., S. latistrigis sp. nov., S. neimengensis sp. nov., S. petilidentis sp. nov. and S. spissus sp. nov. A key to the Chinese species of Sinophorus is provided.

The genus Campoplex Gravenhorst, 1829 (Hymenoptera, Ichneumonidae, Campopleginae) from China.

The genus Campoplex Gravenhorst, 1829 (Hymenoptera, Ichneumonidae, Campopleginae) from China is revised. Thirty-nine new species are proposed (C. absitus sp. nov., C. acarus sp. nov., C. adustantennalis sp. nov., C. angustaulacis sp. nov., C. apacicarinatus sp. nov., C. artivultus sp. nov., C. atricrus sp. nov., C. collucatus sp. nov., C. concretus sp. nov., C. confluentus sp. nov., C. cyclus sp. nov., C. densipunctatus sp. nov., C. exareola sp. nov., C. granalvus sp. nov., C. grandialphus sp. nov., C. grandicella sp. nov., C. granulosus sp. nov., C. galbipedis sp. nov., C. hei sp. nov., C. liuae sp. nov., C. lobatus sp. nov., C. longiclypeus sp. nov., C. maurotrochanter sp. nov., C. medicarinatus sp. nov., C. monochroma sp. nov., C. obtusoclypeus sp. nov., C. parassosae sp. nov., C. perpendicularis sp. nov., C. proportionis sp. nov., C. protenus sp. nov., C. plicopunctatus sp. nov., C. pseudocyclus sp. nov., C. pseudostrigatus sp. nov., C. shanxiensis sp. nov., C. strigatus sp. nov., C. taenius sp. nov., C. tanae sp. nov., C. xizangensis sp. nov., and C. xuthomelonus sp. nov.) and one species is recorded as new to Nepal (C. oriens Gupta Maheshwary). A key to Chinese species of Campoplex is provided.

New species and records of Venturia Schrottky (Hymenoptera, Ichneumonidae, Campopleginae) from China and Nepal.

Four new species of Venturia Schrottky, 1902 (Hymenoptera, Ichneumonidae, Campopleginae) from Oriental China and Nepal are described (V. contiguus sp. nov. and V. yunnanensis sp. nov. from China; V. liuae sp. nov. and V. levocarinata sp. nov. from Nepal). In addition, two species are reported from China (V. serpentina Maheshwary, 1977 and V. inclyta (Morley, 1923)) for the first time and all listed species are illustrated. A key to all species from China and Nepal is provided.

The genus Casinaria Holmgren, 1859 (Hymenoptera: Ichneumonidae, Campopleginae) from China.

The genus Casinaria Holmgren, 1859 (Hymenoptera, Ichneumonidae, Campopleginae) from China is revised. Nine new species are proposed (C. albifunda sp. nov., C. artivultis sp. nov., C. exilis sp. nov., C. exiloides sp. nov., C. hei sp. nov., C. melasoma sp. nov., C. partolstoyi sp. nov., C. remota sp. nov., and C. xui sp. nov.) and two species are recorded as new to China (C. ajanta Maheshwary Gupta and C. varuni Maheshwary Gupta). A key to the Chinese species of Casinaria is provided.

Antiangiogenic therapy in diabetic nephropathy: A double­edged sword (Review).

Diabetes and the associated complications are becoming a serious global threat and an increasing burden to human health and the healthcare systems. Diabetic nephropathy (DN) is the primary cause of end­stage kidney disease. Abnormal angiogenesis is well established to be implicated in the morphology and pathophysiology of DN. Factors that promote or inhibit angiogenesis serve an important role in DN. In the present review, the current issues associated with the vascular disease in DN are highlighted, and the challenges in the development of treatments are discussed.

Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia.

Cordycepin exerted significant neuroprotective effects and protected against cerebral ischemic damage. Learning and memory impairments after cerebral ischemia are common. Cordycepin has been proved to improve memory impairments induced by cerebral ischemia, but its underlying mechanism has not been revealed yet. The plasticity of synaptic structure and function is considered to be one of the neural mechanisms of learning and memory. Therefore, we investigated how cordycepin benefits dendritic morphology and synaptic transmission after cerebral ischemia and traced the related molecular mechanisms. The effects of cordycepin on the protection against ischemia were studied by using global cerebral ischemia (GCI) and oxygen-glucose deprivation (OGD) models. Behavioral long-term potentiation (LTP) and synaptic transmission were observed with electrophysiological recordings. The dendritic morphology and histological assessment were assessed by Golgi staining and hematoxylin-eosin (HE) staining, respectively. Adenosine A1 receptors (A1R) and adenosine A2A receptors (A2AR) were evaluated with western blotting. The results showed that cordycepin reduced the GCI-induced dendritic morphology scathing and behavioral LTP impairment in the hippocampal CA1 area, improved the learning and memory abilities, and up-regulated the level of A1R but not A2AR. In the in vitro experiments, cordycepin pre-perfusion could alleviate the hippocampal slices injury and synaptic transmission cripple induced by OGD, accompanied by increased adenosine content. In addition, the protective effect of cordycepin on OGD-induced synaptic transmission damage was eliminated by using an A1R antagonist instead of A2AR. These findings revealed that cordycepin alleviated synaptic dysfunction and dendritic injury in ischemic models by modulating A1R, which provides new insights into the pharmacological mechanisms of cordycepin for ameliorating cognitive impairment induced by cerebral ischemia.

Construction and Evaluation of Peptide-Linked Lactobacillus brevis ß-Galactosidase Heterodimers.

BACKGROUND: ß-galactosidases are enzymes that are utilized to hydrolyze lactose into galactose and glucose, and are is widely used in the food industry. OBJECTIVE: We describe the recombinant expression of an unstudied, heterodimeric ß-galactosidase originating from Lactobacillus brevis ATCC 367 in Escherichia coli. Furthermore, six different constructs, in which the two protein subunits were fused with different peptide linkers, were also investigated. METHODS: The heterodimeric subunits of the ß-galactosidase were cloned in expressed in various expression constructs, by using either two vectors for the independent expression of each subunit, or using a single Duet vector for the co-expression of the two subunits. RESULTS: The co-expression in two independent expression vectors only resulted in low ß-galactosidase activities, whereas the co-expression in a single Duet vector of the independent and fused subunits increased the ß-galactosidase activity significantly. The recombinant ß-galactosidase showed comparable hydrolyzing properties towards lactose, N-acetyllactosamine, and pNP-ß-D-galactoside. CONCLUSION: The usability of the recombinant L. brevis ß-galactosidase was further demonstrated by the hydrolysis of human, bovine, and goat milk samples. The herein presented fused ß-galactosidase constructs may be of interest for analytical research as well as in food- and biotechnological applications.

A tree shrew model for steroid-associated osteonecrosis.

Osteonecrosis is a common human disease in orthopedics. It is difficult to treat, and half of patients may need artificial joint replacement, resulting in a considerable economic burden and a reduction in quality of life. Hormones are one of the major causes of osteonecrosis and high doses of corticosteroids are considered the most dangerous factor. Because of the complexity of treatment, we still need a better animal model that can be widely used in drug development and testing. Tree shrews are more closely related to primates than rodents. As such, we constructed a successful tree shrew model to establish and evaluate steroid-associated osteonecrosis (SAON). We found that low-dose lipopolysaccharide (LPS) combined with high-dose methylprednisolone (MPS) over 12 weeks could be used to establish a tree shrew model with femoral head necrosis. Serum biochemical and histological analyses showed that an ideal model was obtained. Thus, this work provides a useful animal model for the study of SAON and for the optimization of treatment methods.

Microglial activation in the dorsal striatum participates in anxiety-like behavior in Cyld knockout mice.

CYLD lysine 63 deubiquitinase (CYLD), that is mainly involved in immune responses and inflammation, is expressed at high levels in the brain, especially in the dorsal striatum, but its physiological function of CYLD in the brain remains unexplored. The present study investigated the effect of Cyld gene knockout on behavior relevant to the dorsal striatum, such as motor activity and depression-like and anxiety-like behavior. Microglia and the pro-inflammatory cytokines including interleukin (IL)-1 ß and tumor necrosis factor (TNF)- α were evaluated in the dorsal striatum to elucidate the underlying mechanism. Cyld knockout (Cyld-/-) mice exhibited anxiety-like behavior, but not motor deficits or depression-like behavior. Microglia were activated and the mRNA levels of IL-1 ß and TNF- α were increased in the dorsal striatum of Cyld-/- mice compared to Cyld+/+ mice. The microglial modulator minocycline partially reversed the anxiety-like behavior, microglial activation and increase in IL-1 ß and TNF- α mRNA and protein levels in the dorsal striatum of Cyld-/- mice. Collectively, these results suggest that Cyld knockout leading to microglial activation promotes IL-1 ß and TNF- α expression and acts as a critical pathway in the pathophysiology of anxiety.

Limb-shaking transient ischemic attack with facial muscles involuntary twitch successfully treated with internal carotid artery stenting.

INTRODUCTION: Limb-shaking transient ischemic attack (LS-TIA) is a clinical disease with severe carotid stenosis, which is characterized by unilateral rhythmic dance or tremor like involuntary movements of arms and/or legs, but facial muscles are usually unaffected. METHODS: Today, we report a 42-year-old man with transient ischemic attack who suffered from right limb shaking and right facial muscle twitching due to the obvious stenosis of left internal carotid artery (ICA). Written informed consent was obtained from participants according to the Declaration of Helsinki, and a local ethic committee approved the study. ICA angioplasty and stent implantation were performed as treatment attempts. A brain protection device was navigated through the lesion and placed at the distal end of the stenosis. RESULT: The patient successfully completed the recanalization through stent placement, and the involuntary shaking of limbs and face was improved. During the 3-month follow-up, the patient's symptoms disappeared completely and did not attack again. CONCLUSION: This case report highlights the importance of accurate diagnosis and treatment, because treatment-related carotid artery occlusion can not only eliminate the attack, but also reduce the risk of future stroke.

[Analysis and monitoring of traditional Chinese medicines for tumor based on data mining].

The traditional Chinese medicine(TCM) decoction pieces for treating tumors in China-Japan Friendship Hospital in both outpatient and inpatient departments from January 1 to December 31, 2018 were analyzed in this paper, and the statistical analysis on the frequency and proportion of TCM decoction pieces, as well as the average dosage and dosage range were conducted. Such data were then compared with Chinese Pharmacopoeia. At the same time, data mining association rules were used to study the compatibility of TCM in oncology, and finally, the drug use in TCM was discussed. The top 20(use frequency) TCM decoction pieces for tumors were mainly based on tonic medicines; the use frequency of toxic TCM decoction pieces was low, mainly of small poisonous pieces, with dosage exceeding pharmacopoeia. The drug combinations with higher frequency included Fried Atractylodis Macrocephalae Rhizoma-Poria Cocos(16.11%), and Astragali Radix-Poria Cocos(15.10%). Drug pairs with strong associations included Achyranthes Bidentata→Parasitic Loranthus, Coix Seed→Achyranthes Bidentata, Achyranthes Bidentata→Hairyvein Agrimony, Cuscutae Semen→Achyranthes Bidentata and so on. According to the use of drugs, the drug monitoring can be emphasized from the aspects of usage and dosage, selection of processed TCM, compatibility, decoction methods, and patient education. Pharmacists can analyze the characteristics and regularity of the use of TCM for tumors through data mining methods, and this can be a cutting point for drug monitoring.