The role and mechanism of immunotherapy in pediatric subdural Effusion：Case reports and literature review.

Background: Due to its obscure etiology and diverse clinical manifestations, the treatment of subdural effusion, presents challenges, and the condition's progression to chronic subdural hematoma(cSDH) often necessitates surgical intervention.This study reports on two pediatric patients who developed progressive subdural effusion following minor head injuries. Both cases were notable for the detection of low levels of human herpesvirus in the cerebrospinal fluid, despite other tests returning negative. Immunotherapy led to a dramatic absorption of their subdural effusions, resulting in very positive clinical outcome. Case description: Case 1: This involved a 4-year and 1-month-old boy who was diagnosed with acute cerebellitis due to an unstable gait following a fall. After being discharged, he sustained another minor head injury. A follow-up Magnetic Resonance Imaging (MRI) revealed an increasing and shifting subdural effusion, which was rapidly absorbed following treatment with high doses of methylprednisolone.Case 2: A 6-year and 3-month-old boy presented with headaches following a minor fall. He improved after treatment with intravenous immunoglobulin and low-dose methylprednisolone. The subdural effusion was completely absorbed, and his health remained stable four months after discharge. Conclusion: Our findings suggest that immune inflammation may play a critical role in the development of subdural effusion. The successful treatment outcomes emphasize the potential of immunotherapy as a non-invasive option for managing subdural effusion, particularly in children with unexplained conditions following minor trauma.

Enhancing CO2 storage and marine carbon sink based on seawater mineral carbonation.

Human activities emitting carbon dioxide (CO2) have caused severe greenhouse effects and accelerated climate change, making carbon neutrality urgent. Seawater mineral carbonation technology offers a promising negative emission strategy. This work investigates current advancements in proposed seawater mineral carbonation technologies, including CO2 storage and ocean chemical carbon sequestration. CO2 storage technology relies on indirect mineral carbonation to fix CO2, involving CO2 dissolution, Ca/Mg extraction, and carbonate precipitation, optimized by adding alkaline substances or using electrochemical methods. Ocean chemical carbon sequestration uses natural seawater for direct mineral carbonation, enhanced by adding specific materials to promote carbonate precipitation and increase CO2 absorption, thus enhancing marine carbon sinks. This study evaluates these technologies' advantages and challenges, including reaction rates, costs, and ecological impacts, and analyzes representative materials' carbon fixation potential. Literature indicates that seawater mineral carbonation can play a significant role in CO2 storage and enhancing marine carbon sinks in the coming decades.

NK-92 cells activated by IL-2 inhibit the progression of endometriosis in vitro.

BACKGROUND: Interleukin (IL)-2 is a key cytokine capable of modulating the immune response by activating natural killer (NK) cells. This study was recruited to explore the therapeutic potential of IL-2-activated NK-92 cells in endometriosis in vitro. METHODS: Ectopic endometrial stromal cells (EESCs) were isolated and co-cultured with IL-2-activated NK-92 cells at varying effector-to-target (E:T) ratios (1:0 [Control], 1:1, 1:3, and 1:9). The viability, cytotoxicity, and cell surface antigen expression of IL-2-activated NK-92 cells were assessed. The viability, apoptosis, invasion, and migration ability of EESCs co-cultured with NK-92 cells at different ratios were evaluated. The apoptosis-related proteins, invasion and migration-related proteins as well as MEK/ERK pathway were examined via western blot. Each experiment was repeated three times. RESULTS: IL-2 activation enhanced NK-92 cytotoxicity in a concentration-dependent manner. Co-culturing EESCs with IL-2-activated NK-92 cells at E:T ratios of 1:1, 1:3, and 1:9 reduced EESC viability by 20%, 45%, and 70%, respectively, compared to the control group. Apoptosis rates in EESCs increased in correlation with the NK-92 cell proportion, with the highest rate observed at a 1:9 ratio. Moreover, EESC invasion and migration were significantly inhibited by IL-2-activated NK-92 cells, with a 60% reduction in invasion and a 50% decrease in migration at the 1:9 ratio. Besides, the MEK/ERK signalling pathway was down-regulated in EESCs by IL-2-activated NK-92 cells. CONCLUSION: IL-2-activated NK-92 cells exhibit potent cytotoxic effects against EESCs. They promote EESC apoptosis and inhibit viability, invasion, and migration through modulating the MEK/ERK signalling pathway.

Endometriosis is a common chronic systemic disease affecting approximately 190 million women worldwide. However, clinical treatments for endometriosis remain challenging due to the scarcity of high-quality scientific evidence and conflicting available guidelines. This research was designed to explore whether interleukin (IL)-2 affected the progression of endometriosis by modulating endometrial stromal cell apoptosis and natural killer (NK) cell-mediated cytotoxicity, thereby providing new therapeutic methods for endometriosis.

PERK inhibitor (ISRIB) improves depression-like behavior by inhibitions of HPA-axis over-activation in mice exposed to chronic restraint stress.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.

Pediatric high-altitude pulmonary edema and acute mountain sickness: Clinical features and risk determinants.

OBJECTIVE: This investigation aimed to delineate the clinical manifestations associated with high-altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) in pediatric populations and find the risk factors of HAPE. METHODS: We conducted a retrospective analysis of clinical data from children under 18 years diagnosed with HAPE and AMS at an average altitude of 3000 m. The clinical data between these two groups were compared. RESULTS: The study encompassed 74 pediatric patients, 27 with AMS and 47 with HAPE. HAPE presentations included classic HAPE (55.3%), reentry HAPE (27.7%), and high-altitude resident pulmonary edema (HARPE, 17.0%). Notably, 87.2% of HAPE cases were male, and 68.1% had a high body mass index (BMI). HARPE instances followed viral infections, prominently SARS-CoV-2. HAPE cases exhibited higher BMI, respiratory tract infections within 1 week preceding symptom onset, an increase in white blood cell counts (WBCs), lower peripheral arterial oxygen saturation (SpO2), and higher heart rate compared to the AMS group. Multivariate logistic regression pinpointed high BMI as an independent HAPE risk factor (odds ratio = 19.389, 95% confidence interval: 1.069-351.759, p = .045). CONCLUSION: HAPE occurs predominantly in males, with high BMI identified as a critical independent risk factor. The study underscores the need for heightened awareness and preventive strategies against HAPE in children at high altitudes.

NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence.

BACKGROUND: Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. METHODS: We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit H's (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. RESULTS: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPHErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. CONCLUSIONS: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

Environmental pollution of fluoroquinolones and its relationship with nitrogen cycling mediated by microorganisms.

Fluoroquinolone antibiotics (FQs) are one of the most widely used antibiotics, which are new pollutants with 'pseudo persistence' in the environment, causing great ecological risks. FQs could change the structure and function of microbial communities and affect nitrogen cycling mediated by microorganisms. Consequently, FQs would change the composition of various types of nitrogen in the environment and exert a significant impact on the global nitrogen cycling. We encapsulated the distribution of FQs in the environment and its impacts on nitrogen cycling mediated by microorganisms, explained the role of FQs in each key process of nitrogen cycling, aiming to provide an important reference for revealing the ecological effects of FQs. Generally, FQs could be detected in various environmental media, with significant differences in the concentration and types of FQs in different environments. Ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin are the four types of FQs with the highest detection frequency and concentration. The effect of FQs on nitrogen cycling deeply depends on typical characteristics of concentration and species. FQs mainly inhibit nitrification by reducing the abundance of amoA gene related to ammoxidation process and the abundance and composition of ammoxidation bacteria. FQs inhibits nitrification by reducing the abundance and composition of microbial communities. The denitrification process is mainly inhibited due to the reduction of the activity of related enzymes and the abundance of genes such as narG, nirS, norB, and nosZ genes, as well as the abundance and composition of denitrifying functional microorganisms. The process of anammox is restricted due to the reduction of the abundance, composition and hzo gene abundance of anaerobic anammox bacteria. FQs lead to the reduction of active nitrogen removal and the increase of N2O release in the environment, with further environmental problems such as water eutrophication and greenhouse effect. In the future, we should pay attention to the effects of low concentration FQs and complex antibiotics on the nitrogen cycling, and focus on the effects of FQs on the changes of nitrogen cycle-related microbial monomers and communities.

Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice.

OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg; 30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg; 30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphine-induced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency (T0) and post-treatment latency (T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase (NOS) activity and nitric oxide (NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-D-aspartate (NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups (5, 10, 20 µmol/L, respectively). Except for the control group, cells were treated with NMDA (HT-22 cells: 20 mmol/L; HEK-293 cells: 50 µmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. RESULTS: Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency (0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE (0.05). The combination of berberine and morphine on day one could effectively inhibit the morphine-induced increase of NOS activity and NO content in the spinal cord (0.05). Berberine significantly increased the cell viability of NMDA-induced nerve injury in HT-22 and HEK-293 cells (0.05). Molecular docking showed that berberine binds to the receptor pocket of NMDA. CONCLUSIONS: Berberine could effectively enhance and prolong the duration of morphine analgesia and inhibit the development of morphine-induced tolerance and hyperalgesia. Furthermore, berberine has a certain neuroprotective effect, which may be related to the inhibition of NMDA activity.

Behavioral and ecotoxicology of sulfonamide metabolites in the aquatic environment.

Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.

Biogeochemical behavior and ecological environmental effects of fluoroquinolones.

Synthetic fluoroquinolones (FQs) are the third most commonly used antibiotics in the world and play an extremely important role in antibacterial drugs. The excessive use and discharge will alter ecological environment, with consequence on human health and global sustainable development. It is therefore of great significance for scientific use and management of FQs to systematically understand their biogeochemical behavior and eco-environmental effects. After drug administration in humans and animals, only a small part of FQs are transformed in vivo. The main transformation processes include formylation, acetylation, oxidation and cleavage of piperazine ring, defluorination and decarboxylation of aromatic core ring, etc. About 70% of the original drug and a small amount of transformed products would be migrated to the environment through excretion. After entering the environment, FQs and their transformation products mainly exist in environmental media such as water, soil and sediment, and undergo migration and transformation processes such as adsorption, photolysis and biodegradation. Adsorption facilitates transfer of FQs from medium to another. The photolysis mainly affects the C7-amine substituents of FQs, whereas the core structure of FQs remains intact. Biodegradation mainly refers to the degradation of FQs by microorganisms and microalgae, including piperazine modification of the piperazine ring such as acetylation and formylation, partial or complete ring cleavage, core structure decarboxylation, defluorination and conjugation formation. The migration and transformation processes of FQs cannot completely eliminate them from the environment. Instead, they would become "pseudo-persistent" pollutants, which seriously affect the behavior, growth and reproduction of algae, crustaceans and fish, change biogeochemical cycle, destroy aquatic environment, and stimulate microbial resistance and the generation of resistance genes. In the future, more in-depth studies should be conducted on the environmental behavior of FQs and their impacts on ecological environment, the risk assessment of microbial resistance and resistance genes of FQs, and the mechanism and effect of micro-biodegradation of FQs.

FAM64A aggravates proliferation, invasion, lipid droplet formation, and chemoresistance in gastric cancer: A biomarker for aggressiveness and a gene therapy target.

FAM64A is a mitogen-induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A-related genes were principally categorized into ubiquitin-mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial-mesenchymal transition via the EGFR/Akt/mTOR/NF-κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.

Homeostasis of flavonoids and triterpenoids most likely modulates starch metabolism for pollen tube penetration in rice.

In angiosperms, the timely delivery of sperm cell nuclei by pollen tube (PT) to the ovule is vital for double fertilization. Penetration of PT into maternal stigma tissue is a critical step for sperm cell nuclei delivery, yet little is known about the process. Here, a male-specific and sporophytic mutant xt6, where PTs are able to germinate but unable to penetrate the stigma tissue, is reported in Oryza sativa. Through genetic study, the causative gene was identified as Chalcone synthase (OsCHS1), encoding the first enzyme in flavonoid biosynthesis. Indeed, flavonols were undetected in mutant pollen grains and PTs, indicating that the mutation abolished flavonoid biosynthesis. Nevertheless, the phenotype cannot be rescued by exogenous application of quercetin and kaempferol as reported in maize and petunia, suggesting a different mechanism exists in rice. Further analysis showed that loss of OsCHS1 function disrupted the homeostasis of flavonoid and triterpenoid metabolism and led to the accumulation of triterpenoid, which inhibits significantly α-amylase activity, amyloplast hydrolysis and monosaccharide content in xt6, these ultimately impaired tricarboxylic acid (TCA) cycle, reduced ATP content and lowered the turgor pressure as well. Our findings reveal a new mechanism that OsCHS1 modulates starch hydrolysis and glycometabolism through modulating the metabolic homeostasis of flavonoids and triterpenoids which affects α-amylase activity to maintain PT penetration in rice, which contributes to a better understanding of the function of CHS1 in crop fertility and breeding.

Effectiveness of cognitive behavioural-based interventions for adults with attention-deficit/hyperactivity disorder extends beyond core symptoms: A meta-analysis of randomized controlled trials.

OBJECTIVES: To provide an updated systematic review of randomized controlled studies for the efficacy of cognitive behavioural therapy (CBT) in treating adults with attention-deficit/hyperactivity disorder (ADHD). DESIGN: Meta-analysis. METHODS: PROSPERO registration: CRD42021273633. The methods used aligned with the PRISMA guidelines. Database searches identified CBT treatment outcome studies eligible for conducted meta-analysis. Treatment response was summarized by calculating the standardized mean differences for changes in outcome measures for adults with ADHD. Measures included core and internalizing symptoms and were assessed on the basis of self-reporting and investigator evaluation. RESULTS: Twenty-eight studies met the inclusion criteria. This meta-analysis indicates that CBT for adults with ADHD was effective in reducing both core and emotional symptoms. Decreases in depression and anxiety were predicted by the reduction of core ADHD symptoms. An increase in self-esteem and quality of life were also observed for adults with ADHD who were received CBT. Adults who received either individual or group therapy significantly exhibited a greater reduction of symptoms than those who received active control intervention, received treatment as usual, or were on the treatment waitlist. Traditional CBT was equally effective in reducing core ADHD symptoms but outperformed other CBT approaches in reducing emotional symptoms among adults with ADHD. CONCLUSIONS: This meta-analysis offers cautiously optimistic support for the efficacy of CBT in treating adults with ADHD. The additional reduction of emotional symptoms demonstrates the potential of CBT in adults with ADHD who are at higher risk for depression and anxiety comorbidities.

Investigation of familial tendency of endometriosis / 中华妇产科杂志

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

The roles of ING5 in cancer: A tumor suppressor.

As a Class II tumor suppressor, ING5 contains nuclear localization signal, plant homeodomain, novel conserved region, and leucine zipper-like domains. ING5 proteins form homodimer into a coil-coil structure, and heterodimers with ING4, histone H3K4me3, histone acetyltransferase (HAT) complex, Tip60, Cyclin A1/CDK2, INCA1 and EBNA3C for the transcription of target genes. The acetylated proteins up-regulated by ING5 are preferentially located in nucleus and act as transcription cofactors, chromatin and DNA binding functions, while those down-regulated by ING5 mostly in cytoplasm and contribute to metabolism. ING5 promotes the autoacetylation of HAT p300, p53, histone H3 and H4 for the transcription of downstream genes (Bax, GADD45, p21, p27 and so forth). Transcriptionally, YY1 and SRF up-regulate ING5 mRNA expression by the interaction of YY1-SRF-p53-ING5 complex with ING5 promoter. Translationally, ING5 is targeted by miR-196, miR-196a, miR-196b-5p, miR-193a-3p, miR-27-3p, miR-200b/200a/429, miR-1307, miR-193, miR-222, miR-331-3p, miR-181b, miR-543 and miR-196-b. ING5 suppresses proliferation, migration, invasion and tumor growth of various cancer cells via the suppression of EGFR/PI3K/Akt, IL-6/STAT3, Akt/NF-κB/NF-κB/MMP-9 or IL-6/CXCL12 pathway. ING5-mediated chemoresistance is closely linked to anti-apoptosis, overexpression of chemoresistant genes, the activation of PI3K/Akt/NF-κB and Wnt/ß-catenin signal pathways. Histologically, ING5 abrogation in gastric stem-like and pdx1-positive cells causes gastric dysplasia and cancer, and conditional ING5 knockout in pdx1-positive and gastric chief cells increases MNU-induced gastric carcinogenesis. Intestinal ING5 deletion increases AOM/DSS- induced colorectal carcinogenesis and decreases high-fat-diet weight. The overexpression and nucleocytoplasmic translocation of ING5 are seen during carcinogenesis, and ING5 expression was inversely associated with aggressive behaviors and poor prognosis in a variety of cancers. These findings indicated that ING5 might be used for a molecular marker for carcinogenesis and following progression, and as a target for gene therapy if its chemoresistant function might be ameliorated.

Biofunctional roles of estrogen in coronavirus disease 2019: Beyond a steroid hormone.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), epidemic poses a major global public health threat with more than one million daily new infections and hundreds of deaths. To combat this global pandemic, efficient prevention and management strategies are urgently needed. Together with the main characteristics of COVID-19, impaired coagulation with dysfunctions of the immune response in COVID-19 pathophysiology causes high mortality and morbidity. From recent clinical observations, increased expression of specific types of estrogen appears to protect patients from SARS-CoV-2 infection, thereby, reducing mortality. COVID-19 severity is less common in women than in men, particularly in menopausal women. Furthermore, estrogen levels are negatively correlated with COVID-19 severity and mortality. These findings suggest that estrogen plays a protective role in the pathophysiology of COVID-19. In this review, we discuss the potential roles of estrogen in blocking the SARS-CoV-2 from invading alveolar cells and replicating, and summarize the potential mechanisms of anti-inflammation, immune modulation, reactive oxygen species resistance, anti-thrombosis, vascular dilation, and vascular endothelium protection. Finally, the potential therapeutic effects of estrogen against COVID-19 are reviewed. This review provides insights into the role of estrogen and its use as a potential strategy to reduce the mortality associated with COVID-19, and possibly other viral infections and discusses the possible challenges and pertinent questions.

Metastatic malignant melanoma from anorectum presenting as an isolated breast tumor: A case report and literature review.

RATIONALE: Anorectal malignant melanoma regularly exhibits a biological aggressive behavior which is metastasizing to lung, bone, brain or other organs and tissues early in the course of the disease. Compared with melanoma in the other parts of the body, anorectal malignant melanoma is relatively rare. Metastatic to the breast tissue from anorectal malignant melanoma or from other extra-mammary tumors are very rare. PATIENT CONCERNS: We report the case of a 65-year-old female who suffering from anorectal malignant melanoma and implemented complete surgical resection. Two years later, a space-occupying lesion in the outer upper quadrant of the right breast was observed on a chest CT. DIAGNOSIS: The right breast was excised, and breast metastasis of anorectal malignant melanoma was histologically confirmed. INTERVENTIONS: Radical mastectomy of the right breast was performed, and no lymph nodes or other metastases were observed. OUTCOMES: The patient's operative course was uneventful. The patient completely recovered and transfers to the oncology department for further treatment. LESSON: The patient presented with an isolated breast tumor. Duo to Malignant melanoma could mimic many kind of poorly differentiated tumors, it is difficult to diagnose accurately, especially when it appears as an isolated mammary tumor. Because of the treatment measures and prognosis between malignant melanoma and breast cancer are entirely different.

A chalcone-syringaldehyde hybrid inhibits triple-negative breast cancer cell proliferation and migration by inhibiting CKAP2-mediated FAK and STAT3 phosphorylation.

BACKGROUND: Although triple-negative breast cancer (TNBC) accounts for only 15% of breast cancer cases, it is associated with a high relapse rate and poor outcome after standard treatment. Currently, the effective drugs and treatment strategies for TNBC remain limited, and thus, developing effective treatments for TNBC is pressing. Several studies have demonstrated that both chalcone and syringaldehyde have anticancer effect, but their potential anti-TNBC bioactivity are still unknown. PURPOSE: The present study aimed to synthesize a chalcone-syringaldehyde hybrid (CSH1) and explore its potential anti-TNBC effects and the underlying molecular mechanism. METHODS: Cell cytotoxicity was determined by 3-(4,5-dimethythiazol)-2,5-diphenyltetrazolium bromide (MTT). The activity of cell proliferation was measured by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Cell cycle distribution and cell apoptosis were determined by fluorescence-activated cell sorter (FACS). The situation of DNA damage was observed using fluorescence microscopy. The ability of cell-matrix adhesion, migration and invasion was detected using cell adhesion assay and transwell assay. Transcriptome sequencing was performed to find out the changed genes. Levels of various signaling proteins were assessed by western blotting. RESULTS: CSH1 treatment triggered DNA damage and inhibited DNA replication, cell cycle arrest, and cell apoptosis via suppressing signal transducer and activator of transcription 3 (STAT3) phosphorylation. Whole genome RNA-seq analysis suggested that 4% of changed genes were correlated to DNA damage and repair, and nearly 18% of changed genes were functionally related to cell adhesion and migration. Experimental evidence indicated that CSH1 treatment significantly affected the distribution of focal adhesion kinase (FAK) and its phosphorylation, resulting in cell-matrix-adhesion reduction and migration inhibition of TNBC cells. Further mechanistic studies indicated that CSH1 inhibited TNBC cell proliferation, adhesion, and migration by inhibiting cytoskeleton-associated protein 2 (CKAP2)-mediated FAK and STAT3 phosphorylation signaling. CONCLUSION: These results suggest that CKAP2-mediated FAK and STAT3 phosphorylation signaling is a valuable target for TNBC treatment, and these findings also reveal the potential of CSH1 as a prospective TNBC drug.

The Oncogenic Effects, Pathways, and Target Molecules of JC Polyoma Virus T Antigen in Cancer Cells.

JC polyoma virus (JCPyV) is a ubiquitous polyoma virus that infects the individual to cause progressive multifocal leukoencephalopathy and malignancies. Here, we found that T-antigen knockdown suppressed proliferation, glycolysis, mitochondrial respiration, migration, and invasion, and induced apoptosis and G2 arrest. The reverse was true for T-antigen overexpression, with overexpression of Akt, survivin, retinoblastoma protein, ß-catenin, ß-transducin repeat-containing protein (TRCP), and inhibitor of growth (ING)1, and the underexpression of mammalian target of rapamycin (mTOR), phosphorylated (p)-mTOR, p-p38, Cyclin D1, p21, vascular endothelial growth factor (VEGF), ING2, and ING4 in hepatocellular and pancreatic cancer cells and tissues. In lens tumor cells, T antigen transcriptionally targeted viral carcinogenesis, microRNAs in cancer, focal adhesion, p53, VEGF, phosphoinositide 3 kinase-Akt, and Forkhead box O signaling pathways, fructose and mannose metabolism, ribosome biosynthesis, and choline and pyrimidine metabolism. At a metabolomics level, it targeted protein digestion and absorption, aminoacryl-tRNA biosynthesis, biosynthesis of amino acids, and the AMPK signal pathway. At a proteomic level, it targeted ribosome biogenesis in eukaryotes, citrate cycle, carbon metabolism, protein digestion and absorption, aminoacryl-tRNA biosynthesis, extracellular-matrix-receptor interaction, and biosynthesis of amino acids. In lens tumor cells, T antigen might interact with various keratins, ribosomal proteins, apolipoproteins, G proteins, ubiquitin-related proteins, RPL19, ß-catenin, ß-TRCP, p53, and CCAAT-enhancer-binding proteins in lens tumor cells. T antigen induced a more aggressive phenotype in mouse and human cancer cells due to oncogene activation, inactivation of tumor suppressors, and disruption of metabolism, cell adhesion, and long noncoding RNA-microRNA-target axes.

Efficacy of adrenocorticotropic hormone in children with frequently relapsing or steroid-dependent nephrotic syndrome / 中华儿科杂志

Objective: To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in children with frequently relapsing or steroid-dependent nephrotic syndrome. Methods: The clinical data of 38 children with frequently relapsing or steroid-dependent nephrotic syndrome who were admitted to the Department of Nephrology, the Children Hospital, Zhejiang University School of Medicine from January 2015 to December 2020 were retrospectively analyzed. The general information, clinical manifestations, laboratory data of the children and follow-up (till 12 months after treatment) were collected. The patients were divided into ACTH group and Glucocorticoid (GC) group according to treatment plan. Cumulative remission, average recurrence rate, GC dosage, height and weight change and peripheral blood CD19+B lymphocyte count were compared between the two groups to evaluate the efficacy and adverse reactions of ACTH. Fisher's exact test, t test or rank sum test was used for comparison between groups. Results: Among the 38 patients, 28 were male and 10 were female, aged 84 (24, 180) months; 19 were in ACTH group and 19 were in GC group. The cumulative remission rate of 12 months in ACTH group was higher than that in GC group (9/19 vs. 2/19,χ²=6.81,P=0.009), the average recurrence rate was lower than that in GC group ((0.7±0.8) vs. (1.7±1.1) times, t=-3.27, P=0.011), and the average dosage of GC was lower than that in GC group ((0.27±0.16) vs. (0.51±0.27) mg/(kg·d), t=-3.21, P=0.014). The increase in height was higher than that in the GC group (4 (3,5) vs. 3 (2, 3) cm/year, Z=2.58, P=0.010), and the peripheral blood CD19+B lymphocyte count was lower than that in the GC group ((223±149)×106 vs. (410±213)×106/L,t=-3.35, P=0.009). In safety, 19 cases had transient decreased urine volume, 7 cases had hyperglycemia, and 3 cases had hypertension during the infusion of ACTH, which could be relieved after drug withdrawal. Conclusion: ACTH has a better effect on children with frequently relapsing or steroid-dependent nephrotic syndrome, which can improve cumulative sustained remission rate, lower relapses rate and decrease the dosage of GC, with good safety.