Case report: A rare case of malacoplakia resembling a malignant tumor of the cervix: a case report and review of the literature.

Malacoplakia is a rare chronic granulomatous disease that mostly affects the gastrointestinal tract and urinary tract of immunocompromised patients; malacoplakia rarely effects the female reproductive tract. Here, we report a 56-year-old patient who underwent thymectomy for thymoma and myasthenia gravis prior to developing cervical and vaginal malacoplakia. The patient presented with recurrent vaginal bleeding. We discovered that there were alterations in the cervical cauliflower pattern during colposcopy, which is suggestive of cervical cancer. Pathological examination of the lesion tissue showed that a large number of macrophages aggregated, and M-G bodies with concentric circles and refractive properties were observed between cells. Immunostaining for CD68 and CD163 was positive, and special staining for D-PAS and PAS was positive. The discovery of Escherichia coli in bacterial culture can aid in the diagnosis of malacoplakia. Following surgery, we performed vaginal lavage with antibiotics in addition to resection of local cervical and vaginal lesions. This study provides a fresh perspective on the management of genital malacoplakia.

[Clinical and genetic analysis of a child with X-linked mental retardation due to variant of SLC9A7 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of a child with mental retardation, language and motor developmental delay and epilepsy. METHODS: A child who was admitted to the First Affiliated Hospital of Zhengzhou University in March 2020 for intermittent seizures for over two months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to high throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The clinical manifestations of the child have included mental retardation, language and motor developmental delay, and seizures. High-throughput sequencing revealed that he has harbored a hemizygous splice site variant (NM_032591.3: c.1030-1G>C) of the SLC9A7 gene, which was inherited from his mother and unreported previously. CONCLUSION: The hemizygous splice site variant (NM_032591.3: c.1030-1G>C) of the SLC9A7 gene probably underlay the disease in this child. Above finding has provided a basis for clinical diagnosis and genetic counseling.

A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review.

Background: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases. Methods: For the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis. Case presentation: An 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications. Results: Among the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death. Conclusion: Our findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes.

Maturation of the gut metabolome during the first year of life in humans.

The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and influenced by many postnatal factors, moreover, little is known about the development of the gut metabolome. We showed that geography has an important influence on the microbiome dynamics in the first year of life based on two independent cohorts from China and Sweden. Major compositional differences since birth were the high relative abundance of Bacteroides in the Swedish cohort and Streptococcus in the Chinese cohort. We analyzed the development of the fecal metabolome in the first year of life in the Chinese cohort. Lipid metabolism, especially acylcarnitines and bile acids, was the most abundant metabolic pathway in the newborn gut. Delivery mode and feeding induced particular differences in the gut metabolome since birth. In contrast to C-section newborns, medium- and long-chain acylcarnitines were abundant at newborn age only in vaginally delivered infants, associated by the presence of bacteria such as Bacteroides vulgatus and Parabacteroides merdae. Our data provide a basis for understanding the maturation of the fecal metabolome and the metabolic role of gut microbiota in infancy.

Crosstalk between Breast Milk N-Acetylneuraminic Acid and Infant Growth in a Gut Microbiota-Dependent Manner.

The healthy growth of infants during early life is associated with lifelong consequences. Breastfeeding has positive impacts on reducing obesity risk, which is likely due to the varied components of breast milk, such as N-acetylneuraminic acid (Neu5Ac). However, the effect of breast milk Neu5Ac on infant growth has not been well studied. In this study, targeted metabolomic and metagenomic analyses were performed to illustrate the association between breast milk Neu5Ac and infant growth. Results demonstrated that Neu5Ac was significantly abundant in breast milk from infants with low obesity risk in two independent Chinese cohorts. Neu5Ac from breast milk altered infant gut microbiota and bile acid metabolism, resulting in a distinct fecal bile acid profile in the high-Neu5Ac group, which was characterized by reduced levels of primary bile acids and elevated levels of secondary bile acids. Taurodeoxycholic acid 3-sulfate and taurochenodeoxycholic acid 3-sulfate were correlated with high breast milk Neu5Ac and low obesity risk in infants, and their associations with healthy growth were reproduced in mice colonized with infant-derived microbiota. Parabacteroides might be linked to bile acid metabolism and act as a mediator between Neu5Ac and infant growth. These results showed the gut microbiota-dependent crosstalk between breast milk Neu5Ac and infant growth.

Epilepsy, gut microbiota, and circadian rhythm.

In recent years, relevant studies have found changes in gut microbiota (GM) in patients with epilepsy. In addition, impaired sleep and circadian patterns are common symptoms of epilepsy. Moreover, the types of seizures have a circadian rhythm. Numerous reports have indicated that the GM and its metabolites have circadian rhythms. This review will describe changes in the GM in clinical and animal studies under epilepsy and circadian rhythm disorder, respectively. The aim is to determine the commonalities and specificities of alterations in GM and their impact on disease occurrence in the context of epilepsy and circadian disruption. Although clinical studies are influenced by many factors, the results suggest that there are some commonalities in the changes of GM. Finally, we discuss the links among epilepsy, gut microbiome, and circadian rhythms, as well as future research that needs to be conducted.

GKLF, a transcriptional activator of Txnip, drives microglia activation in kainic acid-induced murine models of epileptic seizures.

Neuroinflammation is a major component of epilepsy. Gut-enriched Kruppel-like factor (GKLF), a transcription factor of Kruppel-like factor family, has been reported to promote microglia activation and mediate neuroinflammation. However, the role of GKLF in epilepsy remains poorly characterized. This study focused on the function of GKLF in neuron loss and neuroinflammation in epilepsy and the molecular mechanism underlying microglia activation induced by GKLF upon lipopolysaccharides (LPS) treatment. An experimental epileptic model was induced by an intraperitoneal injection of 25 mg/kg kainic acid (KA). Lentivirus vectors (Lv) carrying Gklf CDS or short hairpin RNA targeting Gklf (shGKLF) was injected into the hippocampus, resulting in Gklf overexpression or knockdown in the hippocampus. BV-2 cells were co-infected with Lv-shGKLF or/and Lv carrying thioredoxin interacting protein (Txnip) CDS for 48 h and treated with 1 µg/mL LPS for 24 h. Results showed that GKLF enhanced KA-induced neuronal loss, pro-inflammatory cytokine secretion, activation of NOD-like receptor protein-3 (NLRP3) inflammasomes and microglia, and TXNIP expression in the hippocampus. GKLF inhibition showed negative effects on LPS-induced microglia activation, as evidenced by reduced pro-inflammatory cytokine secretion and activation of NLRP3 inflammasomes. GKLF bound to Txnip promoter and increased TXNIP expression in LPS-activated microglia. Interestingly, Txnip overexpression reversed the inhibitory effect of Gklf knockdown on microglia activation. These findings indicated that GKLF was involved in microglia activation via TXNIP. This study demonstrates the underlying mechanism of GKLF in the pathogenesis of epilepsy and uncovers that GKLF inhibition may be a therapeutic strategy for epilepsy treatment.

N6-methyladenosine (m6A) as a regulator of carcinogenesis and drug resistance by targeting epithelial-mesenchymal transition and cancer stem cells.

Emergence of drug resistance to chemotherapeutic agents is the principal obstacle towards curative cancer treatment in human cancer patients. It is in an urgent to explore the underlying molecular mechanisms to overcome the drug resistance. N6-Methyladenosine (m6A) RNA modification is the most abundant reversible RNA modification and has emerged in recent years to regulate gene expression in eukaryotes. Recent evidence has identified m6A is associated with cancer pathogenesis and drug resistance, contributing to the self-renewal and differentiation of cancer stem cell, tumor epithelial-mesenchymal transition (EMT) and tumor metastasis. Here we reviewed up-to-date knowledge of the relationship between m6A modulation and drug resistance. Furthermore, we illustrated the underlying mechanisms of m6A modulation in drug resistance. Lastly, we discussed the regulation of m6A modulation in EMT and cancer stem cells. Hence, it will help to provide significant therapeutic strategies to overcome drug resistance for cancer patients by changing m6A-related proteins via targeting cancer stem cells and EMT-phenotypic cells.

Distinguishable Influence of the Delivery Mode, Feeding Pattern, and Infant Sex on Dynamic Alterations in the Intestinal Microbiota in the First Year of Life.

The delivery mode, the feeding pattern and infant sex significantly influence the development of the infant gut flora. However, the extent to which these factors contribute to the establishment of the gut microbiota at different stages has rarely been studied. The factors that play a dominant role in determining microbial colonization of the infant gut at specific time points are unknown. The purpose of this study was to assess the different contributions of the delivery mode, the feeding pattern and infant sex to the composition of the infant gut microbiome. Here, 213 fecal samples from 55 infants at five ages (0, 1, 3, 6, and 12 months postpartum) were collected, and the composition of the gut microbiota via 16S rRNA sequencing was analyzed. The results showed that the average relative abundances of four genera, Bifidobacterium, Bacteroides, Parabacteroides, and Phascolarctobacterium, were increased in vaginally delivered infants versus cesarean section-delivered infants, while those of ten genera, such as Salmonella and Enterobacter, were reduced. The relative proportions of Anaerococcus and Peptostreptococcaceae were higher in exclusive breastfeeding than in combined feeding, while those of Coriobacteriaceae, Lachnospiraceae and Erysipelotrichaceae were lower. The average relative abundances of two genera, Alistipes and Anaeroglobus, were increased in male infants compared with female infants, whereas those of the phyla Firmicutes and Proteobacteria were reduced. During the first year of life, the average UniFrac distances revealed that the individual difference in the gut microbial composition in vaginally delivered infants was greater than that in cesarean section-delivered infants (P < 0.001) and that infants who received combined feeding had greater individual microbiota differences than exclusively breastfed infants (P < 0.01). The delivery mode, infant sex, and the feeding pattern were the dominant factors determining colonization of the infant gut microbiota at 0 months, from 1 to 6 months, and at 12 months postpartum, respectively. This study demonstrated for the first time that infant sex accounted for the dominant contribution to infant gut microbial development from 1 to 6 months postpartum. More broadly, this study effectively established the extent to which the delivery mode, the feeding pattern and infant sex contribute to the development of the gut microbiota at various time points during the first year of life.

CASPR2 antibody associated neurological syndromes in children.

To strengthen the understanding of the clinical features for CASPR2 neurological autoimmunity in children. A multicenter retrospective and prospective analysis of CASPR2 autoimmunity was conducted. Twenty-six patients were enrolled, including 25 with serum positivity and 3 with cerebrospinal fluid (CSF) positivity; 5 patients were co-positive with anti-NMDAR or anti-GABABR antibodies. Eleven patients (who manifested with refractory epilepsy, psychobehavioral abnormalities or germinoma) presented with low antibody titers, relatively normal MRI/EEG/CSF examinations, and poor response to immunotherapy and were thus considered false positive (42.3%). Fifteen patients were diagnosed with autoimmune encephalitis/ encephalopathy/ cerebellitis (including 1 whose condition was secondary to Japanese encephalitis). The most common symptoms included disorders of consciousness (10/15), fever (8/15), psychological symptoms/abnormal behaviors (8/15), sleep disorders (8/15), seizures (7/15), movement disorders (5/15), autonomic symptoms (5/15). Brain MRI revealed abnormalities in 10 patients (66.7%). Electroencephalography (EEG) recordings revealed a slow wave background in 13 patients (86.7%). Five patients showed elevated WBCs in CSF, and 4 patients showed elevated protein levels in the CSF. Thirteen patients received immunotherapy (rituximab was adopted in 2 cases) and recovered well. Two patients received symptomatic treatment, and the recovery was slow and accompanied by emotional abnormalities and developmental delay. Autoimmune encephalitis is the most common clinical phenotype; it can be secondary to Japanese encephalitis. Rituximab can be used in patients who respond poorly to conventional immunotherapy. The high false-positive rate of anti-CASPR2 in refractory epilepsy and the psychobehavioral abnormalities needs to be explored further.

Correlation between three-dimensional transperineal ultrasound and pelvic floor electromyography in women with stress urinary incontinence.

OBJECTIVES: To investigate the relationships among pelvic floor myoelectric level, ultrasound and stress urinary incontinence in women. MATERIAL AND METHODS: 218 women with SUI and 300 normal women were studied. The main outcomes were to determine the relationship between SUI and high-risk factors, PFM intensity, pelvic floor EMG value, and pelvic floor ultrasound data. RESULTS: In the pelvic floor EMG data, the abnormal rate of type I muscle fibre strength, type I muscle fibre fatigue, type II muscle fibre strength and type II muscle fibre endurance in the SUI group reached more than 50%. The abnormal rates of type I muscle fibre strength and type II muscle fibre strength in the severe SUI group were more significant than those in the mild and moderate SUI. The funnelization of the black neck urethra, bladder neck mobility, posterior angle of the black neck urethra, urinary increment angle and urinary rotation angle of the SUI group were significantly increased. The levator ani muscle in the SUI group was thinner, and the difference was statistically significant. The analysis of the variance results of the overall significance of the regression model were tested, and the final multiple linear regression model was statistically significant. CONCLUSIONS: With the help of a convenient and economic means of the early detection of SUI, the diagnosis rate can be improved so that SUI tendency can achieve a diagnosis and treatment through nonsurgical treatment with fewer complications and a low risk and improve the quality of life of middle-aged and elderly women.

A Retrospective Study on Clinical Features of Childhood Moyamoya Disease.

BACKGROUND: Childhood moyamoya disease (MMD) can lead to progressive and irreversible neurological impairment. Early age at onset is likely associated with a worst prognosis of the disease. The study aims to summarize the clinical characteristics of childhood MMD for supporting the diagnosis and treatment of early MMD. METHODS: A retrospective study was conducted on children aged zero to 16 years who were diagnosed with MMD in the Department of Neurology and neurosurgery of our hospital from October 2016 to April 2020. The clinical characteristics of children with MMD were summarized for analysis, and the distribution of sex and initial attack type among different age groups was determined by data comparison. RESULTS: The study surveyed 114 children (male to female sex ratio of 1:1.07) with MMD, and 6.1% of them had family history. The mean age of onset was 7.15 ± 3.30 years, and the peak age of onset was five to eight years. The most common initial attack type was transient ischemic attack (TIA) (62 cases, 54.4%) with limb weakness. The incidence of the initial attack type in the three age groups was varied (P < 0.05). The result of overall prognosis was good in 86 cases (89.6%). CONCLUSIONS: In this study, MMD cases were mainly ischemic type and TIA was the most common initial attack type. Infant group was more prone to have cerebral infarction, whereas preschool and school-age groups tended to have TIA. The treatments and prognosis of the studied MMD cases were achieved with good outcomes.

The ubiquitin-editing enzyme TNFAIP3 exerts neuroprotective roles in epilepsy rats through repressing inflammation.

The ubiquitin-editing enzyme TNF alpha-induced protein 3 (TNFAIP3) emerges protective roles in neurological disorder, such as cerebral trauma. However, the molecular mechanisms of TNFAIP3 in epilepsy are not very clear. Hereon, the epileptic mouse models and BV2 microglial cellular models were established by kainic acid (KA) and lipopolysaccharide (LPS) respectively. We found that TNFAIP3 was highly expressed in the hippocampus of epileptic mice. Besides, TNFAIP3 overexpression relieved the spatial learning and memory, reduced the hot plate latency, as well as inhibited neuronal apoptosis in KA-treated mice. In vivo and in vitro experiments indicated that inflammation, a key characteristic of epilepsy, was inhibited by TNFAIP3 upregulation, as evidenced by the downregulated expression of pro-inflammatory cytokine interleukin (IL)-1ß and inducible NO synthase (iNOS), along with the decreased levels of NLRP3 inflammasome, which could activate inflammation. Collectively, we infer that TNFAIP3 relieves neuronal injury in epilepsy by suppressing inflammation.

Effect of Breastmilk Microbiota and Sialylated Oligosaccharides on the Colonization of Infant Gut Microbial Community and Fecal Metabolome.

The complex microbiota and sialylated oligosaccharides in breastmilk are important bioactive components that affect the gut microbiota. However, the effect of breastmilk microbiota and sialylated oligosaccharides on the gut microbiota during the neonatal period has been largely overlooked. Here, 16S rRNA gene sequencing and metabolomics analysis were applied to the breastmilk and feces of 69 newborns to clarify the link between breastmilk components and the newborn gut. Results showed that Staphylococcus, Enterococcus, and Bacteroides were commonly shared and positively correlated between breastmilk and the neonatal intestine and they were the main bacteria of breastmilk that interacted with the newborn fecal metabolome. Breastmilk Staphylococcus mainly interacted with amino acids, whereas Bacteroides was involved in the tryptophan, nucleotide, and vitamin metabolism. Breastmilk sialylated oligosaccharides were related to Bacteroides and amino acids of the newborn fecal metabolites. Moreover, Bacteroides was related to the interaction between breastmilk 3'-sialyllactose and newborn fecal metabolites in the mediation effect models. Finally, we pointed out that breastmilk Bacteroides was important in the milk-gut interaction, and it was negatively associated with waist circumference in infants aged 1 year. Our study provides a scientific basis for understanding the role of breastmilk in the development of newborn gut microbiota and metabolome.

[Clinical and genetic analysis of a child with mental retardation autosomal dominant 7].

OBJECTIVE: To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face. METHODS: The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants. RESULTS: The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin. CONCLUSION: The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.

Plasma microRNAs can be a potential diagnostic biomarker for endometriosis.

OBJECTIVES: Plasma microRNAs are considered potential diagnostic biomarkers for endometriosis. Increasing evidence has shown that a huge number of miRNAs are abnormally expressed in endometriosis plasma and play irreplaceable roles in diagnosis. MATERIAL AND METHODS: The aim of our study was to identify the differential expression of circular miRNA by reviewing the PubMed, ScienceDirect, and Cochrane databases between normal women and women with endometriosis and analyzing the miRNA data downloaded from the GEO database. RESULTS: Because of the differential miRNA expression in this review, we evaluated the diagnostic values of the differentially expressed miRNAs, particularly during the menstrual phases. According to the cut-off criteria with |log 2 FC| > 1.0 and P < 0.05, 36 differentially expressed miRNAs were identified, including 13 upregulated miRNAs and 23 downregulated miRNAs. We developed miR-155, miR-574, miR-23a, and miR-520d via a Venn diagram. Functional enrichment analysis considered that the target miRNAs might be involved in various pathways related to endometriosis, including neurotrophin, Hippo, oocyte meiosis, ubiquitin mediated proteolysis, HTLV-Infection, FoxO, and Rap1 signaling pathways. CTNNB1, MYC, and ES R1 of transcription factors were related to the differentially expressed miRNAs. CONCLUSIONS: In summary, our study suggested that a four-miRNA could be included as a prognostic marker in endometriosis.

The Relationship Between Pelvic Floor Function and Sexual Function in Perimenopausal Women.

INTRODUCTION: Perimenopausal women with pelvic floor dysfunction have worse sexual function than women with functional pelvic floor muscle (PFM), especially in terms of libido, orgasm, sexual satisfaction, and total Female Sexual Function Index (FSFI) scores. AIM: To explore the relationship between pelvic floor muscle function, hormone levels and sexual function in perimenopausal women. METHODS: An analytical cross-sectional study was conducted in 252 women aged 40-55 without pelvic floor disease with FSFI, pelvic floor muscle strength and the hormone levels. MAIN OUTCOME MEASURE: The principle aim was to determine the relationships between sexual dysfunction, PFM strength, and hormone levels. RESULTS: In the functional PFM group, the proportion of menopausal hormone therapy was higher. The proportion of overweight in the dysfunctional PFM group was higher, and had more sexual desire disorder, more orgasm disorder, lower sexual satisfaction, and poor FSFI scores. The correlation between PFM strength, sexual function and female sex hormones suggested that PFM strength and libido, sexual satisfaction and FSFI score are significantly positively correlated, while PFM strength and sexual arousal disorder and vaginal lubricity had a positive correlation. In the multivariate analysis of the risk of sexual dysfunction among perimenopausal women, the higher the PFM strength, the lower the risk of sexual dysfunction. CONCLUSIONS: Perimenopausal women with pelvic floor dysfunction have worse sexual function than women with functional PFM, especially in obese women, those with central adiposity, and not using hormone replacement therapy. The PFM strength was weakly positively correlated with sexual arousal, orgasm, sexual satisfaction, and FSFI score. Zhuo Z, Wang C, Yu H, et al. The Relationship Between Pelvic Floor Function and Sexual Function in Perimenopausal Women. Sex Med 2021;9:100441.

miR-141-3p inhibits the activation of astrocytes and the release of inflammatory cytokines in bacterial meningitis through down-regulating HMGB1.

BACKGROUND: Bacterial meningitis (BM) is a serious infectious disease of the central nervous system that often occurs in children and adolescents. Many studies have suggested that microRNAs (miRNAs) are involved in BM. This study aimed to address the effects of miR-141-3p on astrocyte activation and inflammatory response in BM through HMGB1. METHODS: The 3-week-old rats were injected with Streptococcus pneumoniae (SP) into the lateral ventricle to establish a BM model. Loeffler scoring method was used to evaluate the recovery of neurological function. Brain pathological damage was observed by hematoxylin and eosin (H&E) staining. Primary astrocytes were isolated from brain tissues of BM or non-infected SD rats. The levels of TNF-α, IL-1ß, and IL-6 in brain tissues and astrocyte culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The targeting relationship between miR-141-3p and HMGB1 was tested using dual-luciferase reporter assay. The expression of miR-141-3p, HMGB1, and the astrocytic marker glial fibrillary acidic protein (GFAP) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blotting. Methylation-specific PCR (MSP) analysis was performed to measure the methylation status of miR-141 promoter. RESULTS: The results showed that lower Loeffler scores were exhibited in rats with BM. The subarachnoid space of brain tissues of BM rats was widened, and obvious inflammatory cells were observed. miR-141-3p expression was reduced in BM rats and SP-treated astrocytes. Additionally, we found that overexpression of miR-141-3p led to the downregulation of HMGB1, GFAP, and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in astrocytes. Furthermore, the results of dual-luciferase reporter assay confirmed that miR-141-3p directly targeted HMGB1. Overexpression of miR-141-3p inhibited the levels of GFAP, TNF-α, IL-1ß, and IL-6 in astrocytes, which was eliminated by the up-regulation of HMGB1. The results of MSP analysis indicated that miR-141 promoter was highly methylated in brain tissues and astrocytes. DNMT1 was involved in the methylation of miR-141 promoter in BM. CONCLUSION: The present study verified that miR-141-3p affected inflammatory response by suppressing HMGB1 in SP-induced astrocytes and BM rat model.

Circ_0019435 Exerts Its Functions in the Cellular Process of Cervical Cancer via Epigenetically Silencing DKK1 and PTEN.

Cervical cancer (CC) is the most serious gynecological malignancy among women worldwide. As a subtype of noncoding RNAs (ncRNAs), circular RNAs (circRNAs) play important roles in the regulation of gene expression and cancer progression. It was discovered from the cancer-specific circRNA database (CSCD) that circ_0019435 was mainly distributed in the nucleus of HeLa-S3 cells. However, few researches have mentioned circ_0019435 with its function in cancers. The present study uncovered that circ_0019435 was upregulated in CC cells by qRT-PCR. Moreover, circ_0019435 was more stable than its linear isoform-ABCC2. Besides, no regulation of circ_0019435 on ABCC2 and the chemoresistance of CC cells were found. Then, it was unveiled by a series of functional assays including colony formation, trypan blue staining, and transwell invasion assays in that circ_0019435 ablation induced the suppression of proliferation, invasion, and EMT of HeLa and SiHa cells. The subcellular distribution of circ_0019435 was assessed by subcellular fractionation and FISH assay. Furthermore, it was disclosed that circ_0019435 binds to EZH2 to silence DKK1 and PTEN. Finally, rescue assays corroborated that DKK1 and PTEN were involved in circ_0019435-mediated CC cell progression. In conclusion, circ_0019435 regulates DKK1 and PTEN expression at the epigenetic level, thereby influencing the progression of CC cells.

Inhibition of miR-181a-5p reduces astrocyte and microglia activation and oxidative stress by activating SIRT1 in immature rats with epilepsy.

MicroRNAs regulate gene expression at the posttranscriptional level, and this process has been shown to be implicated in the pathological processes of temporal lobe epilepsy. At present, studies about the impact of microRNA-181a (miR-181a) on epilepsy have focused on hippocampal neurons, and the effect of miR-181a on other cells in the hippocampus remains poorly understood. Herein, we explored the role of miR-181a-5p in a lithium-pilocarpine model of epilepticus in immature rats. We found that the hippocampal expression level of miR-181a-5p was increased. Inhibition of miR-181a-5p protected the hippocampus against epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, oxidative stress, mitochondrial function, and cognitive dysfunction. Moreover, miR-181a-5p inhibition exerted a seizure-suppressing effect via SIRT1 upregulation. Overall, our findings reveal the potential role of the miR-181a-5p/SIRT1 pathway in the development of temporal lobe epilepsy, and this pathway may represent a novel target for ameliorating epilepsy and its sequelae.