The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells.

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

Meta-Analysis of Survival Effects of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1).

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50−2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60−2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study.

BACKGROUND: The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls. METHODS: RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA. RESULTS: Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group. CONCLUSIONS: Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.

Content Analysis and Quality Evaluation of Cesarean Delivery-Related Videos on YouTube: Cross-sectional Study.

BACKGROUND: YouTube is one of the most popular open-access video-sharing websites, and it is also used to obtain health care information. Cesarean delivery is the most common major surgical intervention in many countries. Videos related to cesarean delivery have also been uploaded to YouTube. However, no study has explored the overall quality of cesarean delivery videos on the platform. OBJECTIVE: The objective of this study was to analyze the content and evaluate the quality of the most frequently viewed videos related to cesarean delivery that are accessible on YouTube. METHODS: We searched for a total of 18 terms by combining the 6 terms retrieved from Google AdWords and the 3 terms c section, cesarean section, and cesarean delivery, which are used interchangeably. Videos were sorted by view count, and the 100 videos with the highest view counts were chosen. The number of views, duration, likes and dislikes, content type, and source of each video were recorded. In evaluating the quality of the videos, we referred to a previous study. Additionally, we developed a detailed scoring method that comprehensively evaluates the videos related to cesarean delivery by including the necessary information for each element of the cesarean delivery and whether scientific evidence was presented. RESULTS: Of the 100 videos analyzed, the most prevalent content (n=28) was videos that contained the actual surgical procedure of a cesarean delivery, and the most common source of cesarean delivery videos was physicians (n=30). Videos directly related to cesarean delivery, such as explanation of the surgery and the actual surgical procedure, were mainly uploaded by medical groups and scored higher than the videos indirectly related to cesarean delivery, which were mainly uploaded by nonmedical groups. In addition, videos directly related to cesarean delivery were more often uploaded earlier in time, with lower like ratios compared to indirect videos. CONCLUSIONS: YouTube is currently not an appropriate source for patients seeking information on cesarean delivery.

YouTube as a Source of Information and Education on Hysterectomy.

BACKGROUND: Globally, YouTube is one of the most popular websites, and the content is not restricted to entertainment. The purpose of this study was to assess the quality of information in YouTube videos pertaining to hysterectomy. METHODS: We explored YouTube using the search terms "hysterectomy" and "remove uterus." The videos that appeared were sorted using the filter "sort by view count." Of the initial 100 videos, the top 50 videos for each search term were included for review, as determined by the "relevance" filter based on YouTube's algorithm. After excluding 34 videos for various reasons, 66 were included in the final analysis. Each video rated as "useful" was further analyzed for reliability and completeness of information; a set of pre-determined criteria were modified from a previous study and used to grade the quality of videos. RESULTS: The top 66 videos on hysterectomy had a total of 4,679,118 views. Based on authorship, the videos were categorized as follows: videos uploaded by patients, 37%; academic videos, 35%; videos uploaded by physicians, 13%; commercial videos, 4%; and videos uploaded by non-physicians, 2%. The type of content was also categorized: 50% of the videos recorded personal experiences, 23% recorded surgical techniques, 21% involved explanations of the surgery, and 4% were commercial videos. The majority of the videos made by patients were negatively biased toward hysterectomy surgery (71.72%), while the majority of those made by academics or physicians were surgical educational videos for doctors, not patients. CONCLUSION: YouTube is currently not an appropriate source for patients to gain information on hysterectomy. Physicians should be aware of the limitations and provide up-to-date and peer-reviewed content on the website.

The Anti-Inflammatory Effect of Sulforaphane in Mice with Experimental Autoimmune Encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice. RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30 ± 0.15 vs. 1.90 ± 0.18; P = 0.043) and 14th day (1.80 ± 0.13 vs. 2.75 ± 0.17; P = 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice. CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.

Role of DDX53 in taxol-resistance of cervix cancer cells in vitro.

Cancer/Testis antigen DDX53 shows high expression level in various tumors and is involved in anti-cancer drug resistance. However, the functional study of DDX53 in cervix cancer remains unknown. In this study, the role of DDX53 in taxol-resistance of cervix cancer cells was investigated. In taxol-resistant HelaTR cells, DDX53 was significantly increased as compared to the parental HeLa cells. HelaTR cells also showed upregulation of multidrug resistant gene MDR1, invasive characteristics and decreased apoptosis. In addition, increased autophagy level was observed in HelaTR cells. Overexpression of DDX53 in HeLa and SiHa markedly led to greater resistance to taxol and cisplatin, whereas knockdown of DDX53 in HelaTR cells restored sensitivity, demonstrating that DDX53 regulated taxol resistance in cervix cancer cells. DDX53 overexpression in HeLa and SiHa cells enhanced invasion, migration and anchorage independent growth, DDX53 knockdown showed inverse effects in HeLaTR cells. When DDX53 expression was suppressed by siRNA, autophagic flux and drug resistance of HelaTR cells were decreased. In addition, DDX53 was upregulated in cervix cancer tissues from patient with a glassy cell carcinoma of cervix. Taken together, these results suggest that DDX53 plays a critical role in taxol-resistance by activating autophagy and a potential therapeutic target for the treatment of taxol-resistant cervix cancer.

Clinical characteristics of genital chlamydia infection in pelvic inflammatory disease.

BACKGROUND: Chlamydia infection in acute pelvic inflammatory disease (PID) is associated with serious complications including ectopic pregnancy, tubal infertility, Fitz-Hugh-Curtis syndrome and tubo-ovarian abscess (TOA). This study compared clinical and laboratory data between PID with and without chlamydia infection. METHODS: The medical records of 497 women who were admitted with PID between 2002 and 2011 were reviewed. The patients were divided into two groups (PID with and without chlamydia infection), which were compared in terms of the patients' characteristics, clinical presentation, and laboratory findings, including inflammatory markers. RESULTS: The chlamydia and non-chlamydia groups comprised 175 and 322 women, respectively. The patients in the chlamydia group were younger and had a higher rate of TOA, a longer mean hospital stay, and had undergone more surgeries than the patients in the non- chlamydia group. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and CA-125 level were higher in the chlamydia group than in the non-chlamydia group, but there was no significant difference in the white blood cell count between the two groups. The CA-125 level was the strongest predictor of chlamydia infection, followed by the ESR and CRP level. The area under the receiving operating curve for CA-125, ESR, and CRP was 0.804, 0.755, and 0.663, respectively. CONCLUSIONS: Chlamydia infection in acute PID is associated with increased level of inflammatory markers, such as CA-125, ESR and CRP, incidence of TOA, operation risk, and longer hospitalization.

Attitudes Regarding HPV Vaccinations of Children among Mothers with Adolescent Daughters in Korea.

The aim of this study, carried out before the beginning of human papillomavirus (HPV) vaccinations as a National Immunization Program (NIP) in Korea in 2016, is to assess the ranges of perceptions and personal experience and their influences on attitudes regarding HPV vaccinations of children, among mothers of adolescent (9-14 years of age) daughters in Korea. From November 2015 to February 2016, we distributed a written questionnaire to mothers who had daughters aged 9-14 years. The questionnaire consisted of several questions, related to knowledge of HPV, personal experiences of HPV vaccination, and attitudes toward HPV vaccinations of their adolescent daughters. Of the 260 questionnaires distributed, 140 participants returned answered ones. And although only 51% of participants were aware that cervical cancer is highly related with HPV infection, 70% said they were willing to vaccinate their daughters, showing that awareness does not coincide with intention to vaccinate. Among the participants showing negative attitudes, 50% were concerned about the vaccination side effects. The more the participants' pre-knowledge about HPV infection, and about the relationship of HPV to cervical cancer, the more positive their attitudes (P = 0.002, P < 0.001). Our study showed that, as the level of education rose, the proportion of mothers with negative attitudes toward vaccinating their adolescent daughters rose as well. Thus, the provision of correct education by health care providers and accurate information through active advertising may play an important role in increasing the vaccination rate among adolescent girls in Korea.

An unusual case of vulvar schwannoma.

Schwannoma is a benign, solitary, slow-growing neoplasm of the peripheral nerve sheath. These tumors are rarely found in the external genital system, and only a few cases of vulvar schwannoma have been reported. Herein, we report a case of a vulvar schwannoma. A 37-year-old woman presented with a 3-cm-sized painless mass of the vulva which had been present for 3 years. Magnetic resonance imaging (MRI) of the pelvis showed an isolated finding of a 4.6-cm-sized round mass with a well-defined margin in the midline vulvar area. Simple excision of the tumor was undertaken, and histological examination with immunohistochemical testing demonstrated a vulvar schwannoma. Although benign schwannoma only rarely occurs in the vulva and other external areas of female genitalias, we suggest that it should be considered a differential diagnosis for patients that present a vulvar enlargement or mass. Simple surgical resection and follow-up is the most convenient treatment.

Laparoscopic reconstructive surgery is superior to vaginal reconstruction in the pelvic organ prolapse.

BACKGROUND: Our purpose was to provide the clinical advantages of the laparoscopic approach compare to the vaginal approach in correcting uterine and vaginal vault prolapse. METHODS: Between June 2007 and June 2011, 174 women were admitted to HUMC (Hallym University Medical Center) and underwent pelvic reconstructive surgery for prolapsed vaginal vault and uterus. Upon retrospective review of the medical records, 174 of the patients who had symptoms of pelvic organ prolapsed and Baden-Walker prolapse grade ≥ 2 were selected and divided into two groups as follows: vaginal approach group (n=120) and laparoscopic approach group (n=54). We compared the results of clinical outcome by analyzing Student's t-test and χ(2)-test or the Fisher exact test as appropriate. RESULTS: There were significant difference in success rates without reoperation for recurrence as 91.7% (vaginal approach group, n=110) vs 100% (laparoscopic approach group, n=54), p=0.032. Mean follow-up duration was 31.3 ± 7.6 months for vaginal approach group and 29.7 ± 9.7 months for laparoscopic approach group. The Foley catheter indwelling duration (4.7± 1.9 vs 3.4±2.1 days, p< 0.001) and the length of postoperative hospitalization (6.4 ± 2.1 vs 5.0 ± 1.9 days, p <0.001) were significantly longer in vaginal approach group, whereas the operative time was significantly longer (108.2 ± 38.6 vs 168.3 ± 69.7 minutes, p <0.001) in laparoscopic approach group. CONCLUSIONS: Our result suggest there is significantly lower recurrence rate requiring reoperation and less catheterization time but increased operative time for laparascopic sacrocolpopexy.

Surgical outcome and cost comparison between total vaginal hysterectomy and laparoscopic hysterectomy for uteri weighing >500 g.

STUDY OBJECTIVE: To compare surgical outcomes and overall costs of less invasive methods of hysterectomy to treat benign disease including total vaginal hysterectomy (TVH) and total laparoscopic hysterectomy (TLH) in women with a uterus weighing >500 g. DESIGN: Retrospective review of medical records (Canadian Task Force classification III). SETTING: University-associated hospital. PATIENTS: One hundred three women with a uterus weighing >500 g who had undergone either total vaginal hysterectomy (TVH) (n = 52) or total laparoscopic hysterectomy (TLH) (n = 51). MEASUREMENTS AND MAIN RESULTS: Cost data were extracted from the hospital billing system. Patient characteristics, surgical outcomes, and hospital costs were compared between the 2 groups. Patient characteristics were similar in both groups except for a history of surgery (TVH 11.5%, and TLH 37.3%; p = .01). Insofar as surgical outcomes, mean (SD) operative time was shorter in the TVH group compared with the TLH group (110.00 [28.68] minutes vs 180.47 [51.32] minutes; p < .001), and hospital stay was longer (8.08 [0.68] days vs 7.45 [1.03] days; p < .001). Other surgical outcomes including estimated blood loss (p = .20) and decrease in hemoglobin (p = .12) did not differ between the 2 groups. Total hospital costs (converted from Korean won to US dollars) were significantly lower in the TVH group than in the TLH group ($2076.59 [$666.58] vs $2744.03 [$715.76]; p < .001). CONCLUSION: Our data suggest that TVH is a safe and economic procedure even in women with a uterus weighing >500 g. Skilled surgeons should preferentially consider TVH for treatment of benign uterine disease, regardless of uterine size.

In situ vaccination via tissue-targeted cDC1 expansion enhances the immunogenicity of chemoradiation and immunotherapy.

Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is a restriction on cytotoxic T cell immunity if DCs are not present in sufficient numbers in the tumor and draining lymph nodes to take up and present relevant cancer antigens. To address this bottleneck, we developed a therapeutic based on albumin fused with FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that demonstrated superior pharmacokinetic properties compared with Flt3L, including significantly longer half-life, accumulation in tumors and lymph nodes, and cross-presenting-DC expansion following a single injection. We demonstrated that Alb-Flt3L, in combination with standard-of-care chemotherapy and radiation therapy, serves as an in situ vaccination strategy capable of engendering polyclonal tumor neoantigen-specific immunity spontaneously. In addition, Alb-Flt3L-mediated tumor control synergized with immune checkpoint blockade delivered as anti-PD-L1. The mechanism of action of Alb-Flt3L treatment revealed a dependency on Batf3, type I IFNs, and plasmacytoid DCs. Finally, the ability of Alb-Flt3L to expand human DCs was explored in humanized mice. We observed significant expansion of human cross-presenting-DC subsets, supporting the notion that Alb-Flt3L could be used clinically to modulate human DC populations in future cancer therapeutic regimens.

Clinical practice guidelines for cervical cancer: the Korean Society of Gynecologic Oncology guidelines.

This fifth revised version of the Korean Society of Gynecologic Oncology practice guidelines for the management of cervical cancer incorporates recent research findings and changes in treatment strategies based on version 4.0 released in 2020. Each key question was developed by focusing on recent notable insights and crucial contemporary issues in the field of cervical cancer. These questions were evaluated for their significance and impact on the current treatment and were finalized through voting by the development committee. The selected key questions were as follows: the efficacy and safety of immune checkpoint inhibitors as first- or second-line treatment for recurrent or metastatic cervical cancer; the oncologic safety of minimally invasive radical hysterectomy in early stage cervical cancer; the efficacy and safety of adjuvant systemic treatment after concurrent chemoradiotherapy in locally advanced cervical cancer; and the oncologic safety of sentinel lymph node mapping compared to pelvic lymph node dissection. The recommendations, directions, and strengths of this guideline were based on systematic reviews and meta-analyses, and were finally confirmed through public hearings and external reviews. In this study, we describe the revised practice guidelines for the management of cervical cancer.

Tumor suppressor BLU promotes paclitaxel antitumor activity by inducing apoptosis through the down-regulation of Bcl-2 expression in tumorigenesis.

In this current work, we investigated whether BLU could enhance pro-apoptotic activity of chemotherapeutic drugs in ovarian carcinoma cells. A combination with a chemotherapeutic drug showed an additive effect, and this additive effect was supplemented by the enhancement of caspase-3 and -9 activities. BLU and paclitaxel induced cell cycle arrest in the G2/M phase through the reduction of cyclin dependent kinase 1, cyclin B1, while promoting both p16 and p27 expression. In addition, both BLU and paclitaxel enhanced the expression of the pro-apoptotic protein Bax together with the suppression of anti-apoptotic protein Bcl-2, a protein which is well-known for its function as a regulator in protecting cells from apoptosis. As expected, the Bax and p21 activities were enhanced by BLU or paclitaxel, while a combination of BLU and paclitaxel were additively promoted, whereas Bcl-xL and NF-κB including Bcl-2 activity were inactivated. This study has yielded promising results, which evidence for the first time that BLU could suppress the growth of carcinoma cells. Furthermore, both BLU and paclitaxel inhibited the phosphorylation of signaling components downstream of phosphoinositide 3-kinase, such as 3-phosphoinositide-dependent protein kinase 1, and Akt. Also, BLU plus paclitaxel decreased phosphorylation of p70 ribosomal S6 kinase, as well as decreasing the phosphorylation of glycogen synthase kinase-3ß, which is one of the representative targets of the mammalian target of rapamycin signaling cascade. These results provide evidence that BLU enhances G2/M cell cycle arrest and apoptotic cell death through the up-regulation of Bax, p21 and p53 expression.

Is neoadjuvant chemotherapy followed by radical surgery more effective than radiation therapy for stage IIB cervical cancer?

OBJECTIVE: The primary objective of the study was to compare the survival rate of patients who had received neoadjuvant chemotherapy with that of patients who had received radiation therapy for stage IIB cervical cancer. The secondary objective was to analyze the effect of neoadjuvant chemotherapy on pathological prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had received therapy for stage IIB cervical cancer. Based on the primary therapy, 192 patients were divided into 2 groups; patients in the neoadjuvant chemotherapy group (n =103) underwent a type III radical hysterectomy after completion of the neoadjuvant chemotherapy. Patients in the other group (n = 89) were treated with radiation alone or a combination of chemotherapy and radiotherapy. RESULTS: After neoadjuvant chemotherapy, the level of squamous cell carcinoma antigen, tumor size, lymph node involvement, and parametrium involvement were significantly decreased. However, 90.3% of the patients who had received neoadjuvant chemotherapy needed to have adjuvant therapy after radical surgery because of poor pathological prognostic factors. The rate of disease-free survival did not differ significantly between the 2 groups. However, the overall survival rate was significantly lower in the neoadjuvant chemotherapy group for patients who were 60 years or older (P = 0.03). The rates of disease-free survival and overall survival for patients who had a good (complete or partial) response to the neoadjuvant chemotherapy were not significantly higher than the rates for patients in the radiation therapy group. CONCLUSIONS: Although neoadjuvant chemotherapy improved pathological prognostic factors in patients with stage IIB cervical cancer, it was not sufficiently effective to decrease adjuvant therapy. Neoadjuvant chemotherapy also did not improve the rate of patient survival compared to the rate of patient survival in the radiation therapy group.

Intracardiac metastasis from known cervical cancer: a case report and literature review.

Cardiac metastasis from known cervical cancer is rare. Even through a routine check-up, this type of metastasis can present as pulmonary emboli. Suspicion of this diagnosis in an oncology patient with complicating pulmonary emboli but no evidence of deep vein thrombosis is important, especially in cervical cancer patients with extensive pelvic lymph node metastasis and vascular invasion of a primary tumor. Early recognition may aid in improving the prognosis. We present a case of intracardiac metastasis arising from a squamous carcinoma of the cervix in a patient with pulmonary tumor emboli and review other cases from the literature.

Insights from molecular dynamics simulations of TRPV1 channel modulators in pain.

TRPV1 is a nonselective cation channel vital for detecting noxious stimuli (heat, acid, capsaicin). Its role in pain makes it a potential drug target for chronic pain management, migraines, and related disorders. This review updates molecular dynamics (MD) simulation studies on the TRPV1 channel, focusing on its gating mechanism, ligand-binding sites, and implications for drug design. The article also explores challenges in developing modulators, SAR optimization, and clinical trial studies. Efforts have been undertaken to concisely present MD simulation findings, with a focus on their relevance to drug discovery.

Efficacy and Safety of MED-01 Probiotics on Vaginal Health: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4-6 took MED-01 (5.0 × 109 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.

miR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.