Broadening horizons: the role of ferroptosis in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.

Novel radiopaque ethanol injection: physicochemical properties, animal experiments, and clinical application in vascular malformations.

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.

Analysis of delayed initial radioactive iodine therapy and clinical outcomes in papillary thyroid cancer: a two-center retrospective study.

BACKGROUND: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine (RAI) therapy influences clinical outcomes in papillary thyroid carcinoma (PTC). This study aims to evaluate the impact of the timing to initiate RAI therapy on the response in PTC patients. METHODS: We retrospectively included 405 patients who underwent total thyroidectomy and subsequent RAI therapy at two tertiary hospitals in southwest China. Patients were categorized into two groups based on the interval between thyroidectomy and initial RAI therapy, that is, an early group (interval ≤90 days, n  = 317) and a delayed group (interval >90 days, n  = 88). Responses to RAI therapy were classified as excellent, indeterminate, biochemical incomplete, or structural incomplete. Univariate and multivariate analyses were conducted to identify factors associated with a nonexcellent response. RESULTS: Excellent responses were observed in 77.3% of the early group and 83.0% of the delayed group ( P  = 0.252). No significant impact of RAI therapy timing was also observed across all American Thyroid Association risk classification categories. These findings persisted when patients were analyzed separately according to RAI dose (intermediate-dose group: 3.7 GBq [ n  = 332]; high-activity group: ≥5.5 GBq [ n  = 73]), further subdivided by the timing of RAI therapy. Multivariate analysis identified lymph node dissection, RAI dose, and stimulated thyroglobulin as independent risk factors for excellent response ( P  < 0.05). CONCLUSION: The timing of initial RAI therapy following surgery did not significantly affect outcomes in patients with PTC.

Single-cell RNA sequencing explores the evolution of the ecosystem from leukoplakia to head and neck squamous cell carcinoma.

It has been found that progression from leukoplakia to head and neck squamous cell carcinoma (HNSCC) is a long-term process that may involve changes in the multicellular ecosystem. We acquired scRNA-seq samples information from gene expression omnibus and UCSC Xena database. The BEAM function was used to construct the pseudotime trajectory and analyze the differentially expressed genes in different branches. We used the ssGSEA method to explore the correlation between each cell subgroup and survival time, and obtained the cell subgroup related to prognosis. During the progression from leukoplakia to HNSCC, we found several prognostic cell subgroups, such as AURKB + epithelial cells, SFRP1 + fibroblasts, SLC7A8 + macrophages, FCER1A + CD1C + dendritic cells, and TRGC2 + NK/T cells. All cell subgroups had two different fates, one tending to cell proliferation, migration, and enhancement of angiogenesis capacity, and the other tending to inflammatory immune response, leukocyte chemotaxis, and T cell activation. Tumor-promoting genes such as CD163 and CD209 were highly expressed in the myeloid cells, and depletion marker genes such as TIGIT, LAG3 were highly expressed in NK/T cells. Our study may provide a reference for the molecular mechanism of HNSCC and theoretical basis for the development of new therapeutic strategies.

Effect of radiotherapy on head and neck cancer tissues in patients receiving radiotherapy: a bioinformatics analysis-based study.

Radiotherapy is pivotal in treating head and neck cancers including nasopharyngeal, tongue, hypopharyngeal, larynx, maxillary sinus, parotid gland, and oral cancers. It holds the potential for curative effects and finds application in conjunction with chemotherapy, either as a radical method to preserve organ function or as an adjuvant postoperative treatment. We used bioinformatics analysis to investigate the effects of radiotherapy on head and neck cancer tissues in patients who had received radiotherapy. In this study, the expression and mutation profiles of The Cancer Genome Atlas-Head-Neck Squamous Cell Carcinoma were downloaded from the UCSC-Xena database, categorizing patients into two groups-those receiving radiotherapy and those not receiving radiotherapy. Subsequently, differential expression analysis and gene set enrichment analysis (GSEA) were performed. Following this, single-sample GSEA (ssGSEA) scores related to glucose and lipid metabolism were compared between the two groups. Additionally, immune cell infiltration analysis and single-cell verification were performed. Finally, the mutation profiles of the two groups were compared. The analyses revealed that patients receiving radiotherapy exhibited prolonged survival, enhanced apoptosis in head and neck cancer tissue, and diminished keratinocyte proliferation and migration. A comparison of ssGSEA scores related to glucose and lipid metabolism between the two groups indicated a reduction in glycolysis, tricarboxylic acid cycle activity, and fat synthesis in tissues treated with radiotherapy, suggesting that radiotherapy can effectively inhibit tumour cell energy metabolism. Analyses of immune cell infiltration and single-cell verification suggested decreased infiltration of immune cells post-radiotherapy in head and neck cancer tissues. A comparison of mutation profiles revealed a higher frequency of TP53, TTN, and CDKN2A mutations in patients receiving radiotherapy for head and neck cancer. In conclusion, the bioinformatics analyses delved into the effect of radiotherapy on patients with head and neck carcinoma. This study provides a theoretical framework elucidating the molecular mechanisms underlying radiotherapy's efficacy in treating head and neck cancer and presents scientific recommendations for drug therapy following radiotherapy.

Membrane-protected magnetic covalent organic framework for efficient extraction of estrogens in dairy products.

The presence of estrogens residues in dairy products is a growing concern due to their potential health risk. Herein, in this study, we have developed a membrane-protected magnetic solid-phase extraction (MP-MSPE) method that utilized a magnetic adsorbent (Fe3O4@COF-LZU1) with in-situ growth for the efficient extraction of estrone (E1), 17ß-estradiol (E2), and estriol (E3). When combined with HPLC-FLD, this method allows for the efficient detection of estrogens in dairy products. The stability of the MP-MSPE was improved by the presence of a dialysis membrane, which remained a high extraction efficiency (90 %) even after ten reuse cycles. The hydrogen bonding, π-π interactions and pore size effect contribute to the excellent adsorption of three estrogens onto Fe3O4@COF-LZU1. Under optimal conditions, the method exhibits a low detection limit (0.01-0.15 µg L-1), wide linear range (0.1-800 µg L-1), and favorable recoveries (77.3 %-109.4 %) at three concentration levels (10, 50 and 100 µg L-1). This proposed method is characterized by its simplicity, high efficiency and eco-friendliness, making it a promising approach for extracting estrogens from dairy products.

Role of m6A modification in regulating the PI3K/AKT signaling pathway in cancer.

The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a crucial role in the pathogenesis of cancer. The dysregulation of this pathway has been linked to the development and initiation of various types of cancer. Recently, epigenetic modifications, particularly N6-methyladenosine (m6A), have been recognized as essential contributors to mRNA-related biological processes and translation. The abnormal expression of m6A modification enzymes has been associated with oncogenesis, tumor progression, and drug resistance. Here, we review the role of m6A modification in regulating the PI3K/AKT pathway in cancer and its implications in the development of novel strategies for cancer treatment.

Heterotopic pregnancy after assisted reproductive techniques with favorable outcome of the intrauterine pregnancy: A case report.

BACKGROUND: Heterotopic pregnancy (HP) is a rare condition in which both ectopic and intrauterine pregnancies occur. HP is uncommon after natural conception but has recently received more attention due to the widespread use of assisted reproductive techniques (ART) such as ovulation promotion therapy. CASE SUMMARY: Here, we describe a case of HP that occurred after ART with concurrent tubal and intrauterine singleton pregnancies. This was treated successfully with surgery to preserve the intrauterine pregnancy, resulting in the birth of a low-weight premature infant. This case report aims to increase awareness of the possibility of HP during routine first-trimester ultrasound examinations, especially in pregnancies resulting from ART and even if multiple intrauterine pregnancies are present. CONCLUSION: This case alerts us to the importance of comprehensive data collection during regular consultations. It is important for us to remind ourselves of the possibility of HP in all patients presenting after ART, especially in women with an established and stable intrauterine pregnancy that complain of constant abdominal discomfort and also in women with an unusually raised human chorionic gonadotropin level compared with simplex intrauterine pregnancy. This will allow symptomatic and timeous treatment of patients with better results.

Ethanol Embolization of Chest Wall Arteriovenous Malformations: Four-Year Findings.

OBJECTIVES: To summarize the clinical characteristics and investigate the efficacy of ethanol embolotherapy in the treatment of chest well arteriovenous malformation (AVM). Treatment-associated complications were also explored. MATERIALS AND METHODS: Between March 2017 and August 2021, 32 consecutive patients (mean age, 23.7 years; age range, 5-54 years) who underwent ethanol embolotherapy for chest well AVMs under general anesthesia were included in this study. Embolization was performed through a direct puncture, transarterial catheterization, or a combination of the 2 procedures. The mean follow-up duration after the last treatment was 18.0 months (range, 3-42 months). The degree of devascularization on follow-up (assessed using angiography or computed tomography), and the clinical signs and symptoms of AVMs were evaluated as the therapeutic outcomes. The major and minor complications associated with the procedures were recorded. RESULTS: A total of 103 embolization procedures (mean, 3.2; range, 2-7) comprising 101 ethanol embolization and 2 coil embolizations were performed on 32 patients with chest wall AVMs. The AVM nidus was accessed through the transarterial approach alone in 4 patients, by direct puncture in 11, and a combined procedure in 17 patients. Overall, more than 80% of the procedures were performed using the combined approach. Complete AVM devascularization was achieved in 12 (37.5%) patients. Moreover, 76% to 99% AVM was achieved in 18 patients (56.3%), and 50% to 75% in 2 patients (6.3%). Bleeding, pain, heart failure, and cosmetic deformities were the indications for treatment. For 3 patients (3/32, 9.4%) who had bleeding, the treatment stopped the hemorrhage. Complete pain relief was reported in 8 patients (8/32, 25.0%), whereas complete relief from congestive heart failure post-embolization was observed in 5 of the 6 patients with congestive heart failure (5/6, 83.3%). Complete correction of cosmesis deformities after embolization was achieved in 10 patients (10/32, 31.3%). Two patients who underwent surgery to correct persistent deformity after embolization only showed insignificant improvement. In addition, 6 (18.8%) patients developed 13 complications including blister, necrosis, hemothorax, transient hemoglobinuria, and transient pulmonary artery hypertension. CONCLUSIONS: Ethanol embolotherapy is a safe and effective procedure for chest well AVMs. Surgery is required for some patients with residual cosmesis deformity. CLINICAL IMPACT: Currently, there is no standard treatment for chest well AVMs due to their rarity and high heterogeneity. The present study shows that thanol embolotherapy is a safe and clinically effective treatment procedure for the chest well AVMs. Transarterial embolization in combination with direct puncture embolization can reach the AVM nidus. Ethanol embolotherapy can achieve complete obliteration of the AVM nidus in the majority of patients. Surgery may still be needed to correct cosmetic deformity after embolization. The present study provides valuable evidence to inform clinical decision-making.

Egr3 as an important regulator of uterine decidualization through targeting Hand2.

Early growth response 3 (Egr3) is required for embryogenesis, but little understanding is usable about its function in embryo implantation and decidualization. The present study exhibited an obvious localization of Egr3 in luminal epithelium and subluminal stroma at implantation sites. Administration of estrogen brought about a distinct gather of Egr3 mRNA in uterine luminal and glandular epithelia. Meanwhile, Egr3 was visualized in the decidua where it might facilitate the proliferation of stromal cells via Ccnd3 and accelerate stromal differentiation, testifying the significance of Egr3 in decidualization. In ovariectomized mice uteri or stromal cells, progesterone advanced the expression of Egr3 whose obstruction counteracted the inducement of stromal differentiation by progesterone. Consistently, Egr3 mediated the influence of cAMP and heparin-binding EGF-like growth factor (HB-EGF) on the differentiation program. Additionally, cAMP-protein kinase A (PKA) signaling mediated the adjustment of progesterone on Egr3. Impediment of HB-EGF antagonized the ascendance of Egr3 conferred by cAMP. In stromal cells, Egr3 activated the transcription of Hand2 whose promoter region exhibited the binding enrichment of Egr3. Activation of Hand2 relieved the weakness of stromal differentiation by Egr3 hinderance, whereas knockdown of Hand2 neutralized the guidance of Egr3 overexpression on the differentiation program. Collectively, Egr3 was identified as an important regulator of uterine decidualization through targeting Hand2 in response to progesterone/cAMP/HB-EGF pathway.

Transverse testicular ectopia with persistent Mullerian duct syndrome: Report and review of two cases.

Transverse testicular ectopia is a rare anomaly characterized by both testes descending through a single inguinal canal. The objective of this study was to investigate the pathogenesis, diagnosis, and treatment of transverse testicular ectopia (TTE) with persistent Mullerian duct syndrome (PMDS), and to deepen the understanding of the disease in clinical. A retrospective analysis of the clinical manifestation, diagnosis, and treatment of two children suffering from TTE with PMDS was conducted. Previous studies on the characteristics, diagnosis, and treatment of this disease were reviewed. The two patients were treated with laparoscopy-assisted transseptal orchidopexy-inguinal evaluation. After the surgery, the two patients recovered well. The follow-up visits were done 3 months after the operation. An ultrasound examination confirmed that the two patients had testes in the orthotopic position and normal size. TTE with PMDS is an exceedingly rare disease. The patients manifested cryptorchidism on one side; contralateral inguinal hernia was suspected. Detailed physical and ultrasound examinations before the operation are the key to the early diagnosis of TTE. Laparoscopic evaluation is helpful for the diagnosis and finding of other abnormalities. Surgical treatment is the only method to cure the disease; long-term follow-up is needed after TTE operation.

m6A RNA methylation regulator-related signatures exhibit good prognosis prediction ability for head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has become the sixth most common malignant disease worldwide and is associated with high mortality, with an overall 5-year survival rate of less than 50%. Recent studies have demonstrated that aberrantly expressed m6A regulators are involved in multiple biological and pathological processes, including cancers, but the specific mechanisms of m6A regulators in HNSCC are not well elucidated. In this study, we adopted The Cancer Genome Atlas (TCGA)-HNSCC database and performed a consensus clustering analysis to classify the HNSCC samples. Least absolute shrinkage and selection operator (LASSO) regression was applied to construct an m6A signature-based HNSCC risk prediction model. Cell type identification based on estimating relative subsets of RNA transcripts (CIBERSORT) algorithms was adopted to evaluate the immune cell infiltration level in the tumor microenvironment. Based on the expression of m6A regulators in HNSCC, we identified two clusters, cluster 1 (C1) and cluster 2 (C2). C2 showed a better prognosis than C1 and was mainly enriched in the HIPPO, MYC, NOTCH, and NRF signaling pathways. We constructed an m6A signature-based risk score model and classified patients into high- and low-risk score subgroups. The high-risk-score group showed poor clinical characteristics, higher immune infiltration levels, higher chemokine and chemokine receptor expression levels, and lower immune checkpoint gene expression than the low-risk-score subgroup. In conclusion, our comprehensive analysis suggests that the m6A signature-based risk score might function as a good prognostic predictor. Our study may provide novel therapeutic clues and help predict the prognosis of HNSCC.

Construction of a hypoxia-derived gene model to predict the prognosis and therapeutic response of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most common cancer worldwide and has a poor prognosis in the advanced stage. Increasing evidence has shown that hypoxia contributes to genetic alterations that have essential effects on the occurrence and progression of cancers. However, the exact roles hypoxia-related genes play in HNSCC remain unclear. In this study, we downloaded the mRNA expression profiles and clinical data of patients with HNSCC from The Cancer Genome Atlas and Gene Expression Omnibus. Two molecular subtypes were identified based on prognostic hypoxia-related genes using the ConsensusClusterPlus method. ESTIMATE was used to calculate the immune score of each patient. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were used for functional annotation. A prognostic risk model was generated by Cox regression and least absolute shrinkage and selection operator analysis. We identified two distinct molecular subtypes, cluster 1 and cluster 2, based on 200 hypoxia-related genes. Additionally, we identified three hypoxia-immune subgroups (hypoxia-high/immune-low, hypoxia-low/immune-high, and mixed subgroups). The hypoxia-high/immune-low group had the worst prognosis, while the hypoxia-low/immune-high group had the best prognosis. Patients in the hypoxia-low/immune-high group were more sensitive to anti-PD-L1 treatment and chemotherapy than those in the hypoxia-high/immune-low group. Furthermore, we constructed a prognostic risk model based on the differentially expressed genes between the hypoxia-immune subgroups. The survival analysis and time-dependent ROC analysis results demonstrated the good performance of the established 7-gene signature for predicting HNSCC prognosis. In conclusions, the constructed hypoxia-related model might serve as a promising biomarker for the diagnosis and prognosis of HNSCC, and it could predict immunotherapy and chemotherapy efficacy in HNSCC.

Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis.

Background: Subarachnoid hemorrhage (SAH) is a serious neurosurgical emergency with extremely high morbidity and mortality rates. Resveratrol (RES), a natural polyphenolic phytoalexin, is broadly presented in a wide variety of plants. Previous research had reasonably revealed its neuroprotective effects on experimental SAH animal models to some extent. But the results were more controversial. Therefore, we conducted a meta-analysis to evaluate the evidence on the effectiveness of RES in improving outcomes in SAH animal models. Methods: A systematic literature review was conducted in PubMed, EMBASE, and Web of Science databases to incorporate experimental control studies on the efficacy of RES on SAH models into our research. The standardized mean difference (SMD) was used to compare the brain water content (BWC) and neurological score (NS) between the treatment and control groups. Results: Overall, 16 articles published from 2014 to 2022 met the inclusion criteria. The meta-analysis of BWC showed a significant difference in favor of RES treatment (SMD: -1.026; 95% CI: -1.380, -0.672; p = 0.000) with significant heterogeneity (Q = 84.97; I2 = 60.0%; p = 0.000). Further stratified analysis was performed for methodological differences, especially dosage, time of treatments, and time-point of outcome assessment. The meta-analysis of NS showed a significant difference in favor of RES treatment (SMD: 1.342; 95% CI: 1.089, 1.595; p = 0.000) with low heterogeneity (Q = 25.58; I2 = 17.9%; p = 0.223). Conclusion: Generally, RES treatment showed an improvement in both pathological and behavioral outcomes in SAH animal models. The results of this study may provide a reference for preclinical and clinical studies in the future to some extent, with great significance for human health.

TGF-ß Signaling Pathway-Based Model to Predict the Subtype and Prognosis of Head and Neck Squamous Cell Carcinoma.

Background: Although immunotherapy with immune checkpoint therapy has been used to treat head and neck squamous cell carcinoma (HNSCC), response rates and treatment sensitivity remain limited. Recent studies have indicated that transforming growth factor-ß (TGF-ß) may be an important target for novel cancer immunotherapies. Materials and methods: We collected genomic profile data from The Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator method and Cox regression were used to establish a prognostic model. Gene set enrichment analysis was applied to explore biological functions. Tracking of indels by decomposition and subclass mapping algorithms were adopted to evaluate immunotherapy efficiency. Result: We established a seven TGF-ß pathway-associated gene signature with good prediction efficiency. The high-risk score subgroup mainly showed enrichment in tumor-associated signaling such as hypoxia and epithelial-mesenchymal transition (EMT) pathways; This subgroup was also associated with tumor progression. The low-risk score subgroup was more sensitive to immunotherapy and the high-risk score subgroup to cisplatin, erlotinib, paclitaxel, and crizotinib. Conclusion: The TGF-ß pathway signature gene model provides a novel perspective for evaluating effectiveness pre-immunotherapy and may guide further studies of precision immuno-oncology.

miR-30d-5p: A Non-Coding RNA With Potential Diagnostic, Prognostic and Therapeutic Applications.

Cancer is a great challenge facing global public health. Scholars have made plentiful efforts in the research of cancer therapy, but the results are still not satisfactory. In relevant literature, the role of miRNA in cancer has been widely concerned. MicroRNAs (miRNAs) are a non-coding, endogenous, single-stranded RNAs that regulate a variety of biological functions. The abnormal level of miR-30d-5p, a type of miRNAs, has been associated with various human tumor types, including lung cancer, colorectal cancer, esophageal cancer, prostate cancer, liver cancer, cervical cancer, breast cancer and other types of human tumors. This reflects the vital function of miR-30d-5p in tumor prognosis. miR-30d-5p can be identified either as an inhibitor hindering the development of, or a promoter accelerating the occurrence of tumors. In addition, the role of miR-30d-5p in cell proliferation, motility, apoptosis, autophagy, tumorigenesis, and chemoresistance are also noteworthy. The multiple roles of miR-30d-5p in human cancer suggest that it has broad feasibility as a biomarker and therapeutic target. This review describes the connection between miR-30d-5p and the clinical indications of tumors, and summarizes the mechanisms by which miR-30d-5p mediates cancer progression.

Network pharmacology-based approach to investigate the mechanisms of Zingiber officinale Roscoe in the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDDs) are chronic neurological disorders associated with cognitive or motor dysfunction. As a common spice, Zingiber officinale Roscoe has been used as a medicine to treat a variety of NDDs. However, at the molecular level, the mechanisms of Z. officinale in treating of NDDs have not been deeply investigated. In this study, network pharmacology method, molecular docking, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the mechanisms of Z. officinale in the treatment of NDDs. After a series of biological information analyses, five core targets were obtained, including heme oxygenase 1 (HMOX1), acetylcholinesterase (AChE), nitric oxide synthase (NOS), catechol-O-methyl-transferase (COMT), and metabotropic glutamate receptor 5 (mGluR5). Compounds 75, 68, 46, 67, 69, 49, 66, 50, 34, and 64 were identified as the main components of Z. officinale in the treatment of NDDs. The crucial pathways mainly include neuroactive ligand-receptor signaling pathways, cyclic adenosine monophosphate signaling pathways, dopamine synaptic signaling pathways, and so on. Besides, in vitro experiments by AChE inhibitory activities assay and neuroprotective activities against H2 O2 -induced injury in human neuroblastoma SH-SY5Y cells validated the reliability of the results of network analysis. PRACTICAL APPLICATIONS: Zingiber officinale Roscoe is widely used as a traditional spice and herbal medicine. It contains a number of active ingredients, which have shown activities on anti-neurodegenerative diseases (NDDs). In this paper, the potential mechanism of Z. officinale in the treatment of NDDs is explored through network pharmacology, and it was verified by in vitro experiments. The mechanism was not only clarified at the system level but also proved to be effective at the biological level. The results can be used as a reference for Z. officinale in the treating of NDDs.

[Therapeutic effect of Heirong Kidney-Tonifying Granule on busulfan-induced dyszoospermia in model mice].

OBJECTIVE: To explore the therapeutic effect of Heirong Kidney-Tonifying Granule (HKTG) on busulfan-induced dyszoospermia in mice, and its mechanism in regulating testicular spermatogenesis. METHODS: Forty-eight male mice were randomly divided into six groups of an equal number: blank control (BC), negative control (NC), HKTG-1, HKTG-2, HKTG-3 and HKTG-4. The model of dyszoospermia was established in the latter five groups by intraperitoneal injection of busulfan at 40 mg/kg and, 30 days after modeling, the mice in the BC and NC groups were given gavage of normal saline, and those in the latter four groups treated with HKTG + pilose antler at 400 mg/kg/d, HKTG + pilose antler at 800 mg/kg/d, HKTG + black ants at 400 mg/kg/d and HKTG + black ants at 800 mg/kg/d, respectively, all for 5 consecutive weeks. The mean body weight of the mice was recorded daily, and their testes weighed after treatment. The microstructure of the testis tissue was detected by HE staining, and the localization and expression of spermatogenesis markers in the testis were determined by immunofluorescence staining. RESULTS: The mice in the BC and NC groups showed no statistically significant difference from those in the HKTG groups in the body weight and daily body weight gain (P > 0.05). Compared with the NC mice, the animals in the HKTG-1 group exhibited significantly increased testis weight (P < 0.05), and those in the HKTG-1 and HKTG-1 groups presented a large number of germ cells in the seminiferous tubules, including deformed sperm cells in the lumen, and some seminomatogonia in the seminogenic tubules, but almost no deformed sperm cells. The expressions of the total germ cell marker gene Ddx4, spermatogonial cell marker gene Dazl, spermatic cell marker gene Sycp3 and sperm cell marker gene Tnp1 were significantly upregulated (P < 0.05) while that of the Sertoli cell marker gene Sox9 downregulated (P < 0.05) in the HKTG-1 group. The number of Sertoli cells in the HKTG-1 group was remarkably reduced (P<0.05), corresponding to the increased number of germ cells in the HKTG-1 group. There were no significant changes in the relative expressions of the DDX4, Dazl, Sycp3 and Tnp1 genes, nor in the number of Sertoli cells in the HKTG-3 and HKTG-4 groups. The expressions of meiosis-related genes Meioc, Stra8 and Spo11were markedly upreguated in the HKTG-1 group, indicating significantly improved spermatogenesis in the testis tissue of the mice. CONCLUSION: HKTG improves the function of spermatogenic cells and increases sperm production in the testis tissue of mice by promoting meiosis.

Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma.

BACKGROUND: Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD). METHODS: The transcriptome data and clinical variables of COAD patients were downloaded from TCGA database. The genes in GOBP_AGING gene set was used for prognostic evaluation by the univariate and multivariate Cox regression analyses. The model was presented by a nomogram and assessed by the Kaplan-Meier curves and calibration curves. The drug response and gene mutation were also performed to implicate the clinical significance. The GO and KEGG analyses were employed to unravel the potential functional mechanism. RESULTS: The Gene Set Enrichment Analysis result indicates that GOBP_AGING pathway is significantly enriched in COAD samples. Four aging-related genes are finally used to construct the aging-related prognostic signature: FOXM1, PTH1R, KL, and CGAS. The COAD patients with high risk score have much shorter overall survival in both train cohort and test cohort. The nomogram is then assembled to predict 1-year, 3-year, and 5-year survival. Patients with high risk score have elevated infiltrating B cell naïve and attenuated cisplatin sensitivity. The mutation landscape shows that the TTN, FAT4, ZFHX4, APC, and OBSCN gene mutation are different between high risk score patients and low risk score patients. The differentially expressed genes between patients with high score and low score are enriched in B cell receptor signaling pathway. CONCLUSION: We constructed an aging-related signature in COAD patients, which can predict oncological outcome and optimize therapeutic strategy.

A crucial role for the long non-coding RNA CASC11 in the pathogenesis of human cancers.

Long non-coding RNAs (lncRNAs) are non-coding RNAs more than 200 nucleotides in length. Although they do not encode proteins, lncRNAs can regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging data show that lncRNAs are important for tumorigenesis and cancer progression. Cancer susceptibility candidate 11 (CASC11) is a prominent lncRNA that is upregulated in various types of cancers. Moreover, its overexpression correlates with larger tumor size, more advanced cancer stages, cancer metastasis, and poor overall survival for most types of cancer. Functionally, the knockdown of CASC11 can inhibit cell proliferation, invasion, and migration, while enhancing apoptosis through its regulation of gene expression and signaling pathways and its interactions with functional proteins. Here, we discuss the identification, expression, and function of CASC11. Additionally, we discuss the potential roles of CASC11 as a diagnostic biomarker, prognostic biomarker, and therapeutic target in various cancers.