Association between KRAS and PIK3CA Mutations and Progesterone Resistance in Endometriotic Epithelial Cell Line.

Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.

Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation Analysis.

BACKGROUND: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination. METHODS: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed. RESULTS: Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis. CONCLUSIONS: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.

The Case of an Endometrial Cancer Patient with Breast Cancer Who Has Achieved Long-Term Survival via Letrozole Monotherapy.

Herein, we present the successful treatment of a 92-year-old woman who experienced recurrent EC in the vaginal stump and para-aortic lymph nodes. The patient was first treated with paclitaxel and carboplatin for recurrent EC, which was abandoned after two cycles of chemotherapy because of G4 hematologic toxicity. Later, the patient was treated with letrozole for early-stage breast cancer, which was diagnosed simultaneously with EC recurrence. After four months of hormonal therapy, a partial response was observed not only in the lesions in the breast, but also those in the vaginal stump and para-aortic lymph nodes. She had no recurrence of breast cancer or EC, even after six years of treatment with letrozole-based hormonal therapy. Subsequent whole-exome sequencing using the genomic DNA isolated from the surgical specimen in the uterine tumor identified several genetic variants, including actionable mutations, such as CTNNB1 (p.S37F), PIK3R1 (p.M582Is_10), and TP53 c.375 + 5G>T. These data suggest that the efficacy of letrozole is mediated by blocking the mammalian target of the rapamycin pathway. The findings of this study, substantiated via genetic analysis, suggest the possibility of long-term disease-free survival, even in elderly patients with recurrent EC, which was thought to be difficult to cure completely.

Acidophilic microorganisms in remediation of contaminants present in extremely acidic conditions.

Acidophiles are a group of microorganisms that thrive in acidic environments where pH level is far below the neutral value 7.0. They belong to a larger family called extremophiles, which is a group that thrives in various extreme environmental conditions which are normally inhospitable to other organisms. Several human activities such as mining, construction and other industrial processes release highly acidic effluents and wastes into the environment. Those acidic wastes and wastewaters contain different types of pollutants such as heavy metals, radioactive, and organic, whose have adverse effects on human being as well as on other living organisms. To protect the whole ecosystem, those pollutants containing effluents or wastes must be clean properly before releasing into environment. Physicochemical cleanup processes under extremely acidic conditions are not always successful due to high cost and release of toxic byproducts. While in case of biological methods, except acidophiles, no other microorganisms cannot survive in highly acidic conditions. Therefore, acidophiles can be a good choice for remediation of different types of contaminants present in acidic conditions. In this review article, various roles of acidophilic microorganisms responsible for removing heavy metals and radioactive pollutants from acidic environments were discussed. Bioremediation of various acidic organic pollutants by using acidophiles was also studied. Overall, this review could be helpful to extend our knowledge as well as to do further relevant novel studies in the field of acidic pollutants remediation by applying acidophilic microorganisms.

Enhancing maize's nitrogen-fixing potential through ZmSBT3, a gene suppressing mucilage secretion.

Maize (Zea mays) requires substantial amounts of nitrogen, posing a challenge for its cultivation. Recent work discovered that some ancient Mexican maize landraces harbored diazotrophic bacteria in mucilage secreted by their aerial roots. To see if this trait is retained in modern maize, we conducted a field study of aerial root mucilage (ARM) in 258 inbred lines. We observed that ARM secretion is common in modern maize, but the amount significantly varies, and only a few lines have retained the nitrogen-fixing traits found in ancient landraces. The mucilage of the high-ARM inbred line HN5-724 had high nitrogen-fixing enzyme activity and abundant diazotrophic bacteria. Our genome-wide association study identified 17 candidate genes associated with ARM across three environments. Knockouts of one candidate gene, the subtilase family gene ZmSBT3, confirmed that it negatively regulates ARM secretion. Notably, the ZmSBT3 knockout lines had increased biomass and total nitrogen accumulation under nitrogen-free culture conditions. High ARM was associated with three ZmSBT3 haplotypes that were gradually lost during maize domestication, being retained in only a few modern inbred lines such as HN5-724. In summary, our results identify ZmSBT3 as a potential tool for enhancing ARM, and thus nitrogen fixation, in maize.

Neutropenic enterocolitis-induced sepsis and disseminated intravascular coagulation after chemotherapy: a case report.

BACKGROUND: Neutropenic enterocolitis (NE) is a potentially life-threatening disease that primarily occurs in cancer patients treated with chemotherapy. NE has substantial morbidity and mortality, and its incidence has increased with the widespread use of chemotherapeutic agents such as taxanes, gemcitabine, and leucovorin in patients with lung, breast, gastric, and ovarian cancers. Sometimes NE can be a possible cause of death. Although, conservative approaches are often successful, there are currently no standardized treatment guidelines for NE and it is unclear when such strategies should be implemented. Therefore, we present this report to provide a greater insight into the possible treatment of NE. CASE PRESENTATION: We report the case of a 72-year-old woman with endometrial cancer who was undergoing treatment for hypertension, obesity and diabetes mellitus. The patient initially developed paralytic ileus on the 6th postoperative day (POD) after surgery for endometrial serous carcinoma. Complete recovery was achieved after 4 days of fasting and fluid replacement therapy. On the 27th POD, she received the first cycle of combination chemotherapy consisting of paclitaxel and carboplatin. On day 5 of chemotherapy, she developed the systemic inflammatory response syndrome including febrile neutropenia and sepsis. She then developed disseminated intravascular coagulation (DIC) and septic shock. The patient was subsequently moved to the intensive care unit (ICU). Despite initiating the standard treatment for septic shock and DIC, her overall status worsened. It was assumed that gut distention had led to bowel damage, subsequently leading to bacterial translocation. Thus, she developed NE with severe DIC and septic shock. We decided to reduce the intestinal pressure using an ileus tube to suction the additional air and fluid, even though doing so had a risk of worsening her general condition. The inflammatory reaction subsided, and her general condition improved. The patient recovered after 18 days in the ICU and was discharged alive. CONCLUSIONS: Herein, we describe a patient with suspected chemotherapy-associated NE. Our observations suggest that postoperative ileus may be one of the possible causes of NE. Patients who experience postoperative ileus must be carefully monitored while undergoing chemotherapy.

Nrf2 inhibition induces oxidative stress, renal inflammation and hypertension in mice.

Oxidative stress and renal inflammation play a pivotal role in the pathogenesis of hypertension. The redox-sensitive transcription factor, nuclear factor E2-related factor 2 (Nrf2) is the master regulator of phase II antioxidant enzymes that protects against oxidative stress and inflammation. This study aimed to investigate the effect of Nrf2 inhibition on oxidative stress-associated hypertension and renal dopamine 1 receptor (D1R) dysfunction in mice. Male C57BL/6 J mice were treated with a pro-oxidant, L-buthionine sulfoximine (BSO) (10 mmol/L in drinking water), and ML385 (10 kg body weight/kg body weight/day, intraperitoneally), a novel Nrf2 inhibitor that blocks Nrf2 regulated downstream target genes expression. Mice treated with BSO exhibited oxidative stress, renal functional impairment, inflammation, and elevated blood pressure. Also, BSO treatment increased the activity of phase II antioxidant enzyme, NAD(P)H: quinone oxidoreductase-1 (NQO-1). BSO and ML385 co-treatment exhibited a robust increase in blood pressure, oxidative stress and intensified the renal function deterioration as indicated by a significant increase in serum creatinine, urinary albumin excretion rate, and albumin to creatinine ratio and decreased glomerular filtration rate (GFR). Also, BSO and ML385 co-treatment downregulated NQO-1 and significantly altered the inflammatory cytokines, IL-1ß and IL-10 levels. A D1R agonist SKF38393 failed to promote urinary sodium excretion indicating functional impairment in renal D1R. ML385 per se did not affect mean arterial pressure, GFR, and renal D1R function. Taken together, we concluded that the Nrf2 inhibition aggravated oxidative stress and inflammation by diminishing phase II antioxidant defense that deteriorates renal function and contributes to the development of hypertension in mice.

Effects of Aloe vera Flower Extract and Its Active Constituent Isoorientin on Skin Moisturization via Regulating Involucrin Expression: In Vitro and Molecular Docking Studies.

Skin moisturization is very crucial for maintaining the flexibility, viscoelasticity, and differentiation of the epidermis and its deprivation causes several diseases from dry skin to dermatitis. Aloe vera, a miracle plant having diverse medicinal properties including skin moisturization effects. This study investigated for the first time the molecular mechanism targeting skin moisturization effects of the Aloe vera flower and its major active constituent. By treating human epidermal keratinocytes (HaCaT cells) with Aloe vera flower water extract (AFWE), we found that AFWE upregulated epidermal involucrin by activating the expression of protein kinase C, p38, and ERK 1/2. Additionally, it modulated filaggrin, increased aquaporin expression, and hyaluronan synthesis via a balanced regulation of HAS1 and HYAL1 protein. Similarly, it was able to protect UVB-induced photodamage. Western blot analysis, ELISA, and qRT- PCR were performed to evaluate various epidermal differentiation markers and moisturization-related factors on human epidermal keratinocytes (HaCaT cells). TLC and HPLC were used to detect and analyze the chemical constituents. Among them, we found that an active component of Aloe vera flower, isoorientin (IO) has a high binding affinity to all of its targeted proteins such as involucrin, PKC, P38, etc. through molecular docking assay. This study indicated that the Aloe vera flower and its active constituent, IO can be used as a prominent ingredient to enhance skin barrier function and improve its related pathologies.

Comparison between bidirectional Stratafix® barbed suture and conventional suture in laparoscopic myomectomy: a retrospective study.

BACKGROUND: Laparoscopic myomectomy (LM) is one of the techniques feasible for the treatment of intramural myoma. This technique is reported to be difficult when large fibroids are involved because of excessive blood loss during surgery. Skillful and fast suturing appears to be associated with reduced blood loss during LM. In this study we compared the surgical outcomes of using bidirectional Stratafix® barbed suture versus conventional suture during LM. METHODS: This retrospective study included all patients who underwent LM for the treatment of intramural myoma in our institution between 2015 and 2020. The patients were divided into 2 groups according to the technique of suturing during LM: Group 1 comprised patients in whom Stratafix® barbed suture was used (n = 29), and group 2 comprised those in whom conventional suture was used (n = 15). Data of patient age, myoma size, the number of myoma nodes, hemoglobin levels, total operation time, total suturing time, and blood loss during surgery were compared between the 2 groups. RESULTS: No significant differences in age (p = 0.463) or myoma size (P = 0.373) were observed between the 2 groups. Operation time (P = 0.0104), suturing time (P = 0.007), and blood loss (P = 0.0375) during surgery were significantly less with Stratafix® barbed suture than with conventional suture. No patient required intraoperative transfusion or conversion to laparotomy. CONCLUSION: The use of bidirectional barbed suture reduces operation time, suturing time, and blood loss. As these new sutures have barbs, no knot-tying is required; thus, continuous suturing becomes very simple and maintaining hemostasis is easy. Unskilled gynecological surgeons who apply this suture technique can also perform LM easily. As the bidirectional barbed suture has multiple points of fixation, this suture technique can reapproximate tissue securely, which reduces the chances of reoperation because of proper suture knotting. Therefore, bidirectional Stratafix® barbed sutures could be an optimal and efficient alternative to conventional sutures for use by gynecological surgeons in Japan.

High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.

PURPOSE: The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. Programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 may be used as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of patients with CA and their response to immune checkpoint inhibition therapy. METHODS: In the present study, the clinical stage for all 82 patients with cervical adenocarcinoma was classified according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO); there were 5, 48, 5, 14, 8, and 2 patients with stage IA, IB, IIA, IIB, IIIB, and IVB disease, respectively. The levels of PD-1, PD-L1, and CD8 were analyzed by the immunohistochemical analysis of the formalin-fixed paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed using the Kaplan-Meier method and univariate and multivariate Cox proportional hazard regression models. RESULTS: We observed a significant inverse correlation between the expression of PD-1 and CD8 (p = 0.001, chi-square test). We also found a significant inverse correlation between the expression of PD-L1 and CD8 (p = 0.027). The overall survival and progression-free survival rates were significantly worse in patients with positive PD-1 expression (p = 0.031; p = 0.087, respectively). CONCLUSION: Our results suggest that a high PD-1 expression is associated with a poor prognosis in patients with CA. Further research is necessary to identify the molecular mechanisms that mediate this association.

Mucinous borderline ovarian tumors with BRAFV600E mutation may have low risk for progression to invasive carcinomas.

PURPOSE: Mucinous ovarian carcinomas (MOCs) are relatively rare. It has been proposed that a subset of mucinous cystadenomas (MCAs) may progress to mucinous borderline tumors (MBTs), and then to MOCs. KRAS is the predominantly mutated gene in MOC; however, other associated mutations and the mechanism underlying carcinogenesis in MOC remain unclear. Here, we assessed molecular genetic alterations in mucinous ovarian tumors and constructed mutation profiles. METHODS: Using the Sanger sequencing method, we assessed genetic mutations (KRAS, BRAF, TP53, and PIK3CA) in 16 cases of MOC, 10 cases of MBT, and 12 cases of MCA. RESULTS: Among MOC cases, the prevalence of G12D and G13D KRAS mutations was 43.8% (7/16). No MOC cases showed V600E BRAF and TP53 mutations. Among MBT cases, the prevalence of G12D KRAS mutation was 20.0% (2/10), those of TP53 and PIK3CA mutations were nil, and that of V600E BRAF mutation was 40% (4/10). None of the genetic mutations assessed were detected among MCA cases. CONCLUSION: These results suggest that MBT with V600E BRAF mutation may rarely progress to MOC, while MBT with G12D or G13D KRAS mutation may more commonly progress to MOC.

Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates.

Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.

Displaced Rohingya children at high risk for mental health problems: Findings from refugee camps within Bangladesh.

BACKGROUND: The 2017 political violence against the Rohingya people in the state of Rakhine resulted in a large influx of displaced populations into Bangladesh. Given harsh conditions and experiences in Myanmar, and the harrowing journey to the border, raised levels of child neurodevelopmental disorders (NDDs) and mental health problems were expected. METHODS: A team of child development professionals, physicians, psychologists, and developmental therapists screened 622 children in clinics within the refugee camps using the Developmental Screening Questionnaire (DSQ; 0-<2 years), and the Ten Questions Plus (TQP) for NDDs, and Strengths and Difficulties Questionnaire (SDQ; 2-16 years) for mental health problems. Any child positive on the DSQ or the TQP was assessed for NDDs. RESULTS: Only 4.8% children aged 0-<2 years and 7.3% children aged >2-16 years screened positive for NDDs, comparable with a local Bangladesh population. However, 52% of children were in the abnormal range for emotional symptoms on the SDQ, and 25% abnormal for peer problems. Significant risk factors were being parentless and having lost one or more family members in the recent crisis. CONCLUSIONS: This screening study provides objective evidence of the urgent need for psychosocial support of Rohingya children within camps, with special attention to those without parents, including monitoring of their well-being and counselling of families and other care providers.

Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future.

Ovarian cancer has the worst prognosis among gynecological cancers. Thus, new ovarian cancer treatment strategies are needed. Currently, immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibody are attracting attention worldwide. The Food and Drug Administration approved the use of the PD-1 antibody pembrolizumab for solid cancers with microsatellite instability (MSI)-H or mismatch repair (MMR) deficiency in 2017. However, few studies on ovarian carcinoma have evaluated the relationship among MSI status, lymphocyte infiltration into the tumor, and the expression of immune checkpoint molecules by histologic type. We evaluated the expression of MMR proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunohistochemistry in 136 ovarian cancer patients (76, 13, 23, and 24 cases were high-grade serous, mucinous, endometrioid, and clear cell carcinoma, respectively) to investigate the effectiveness of immune checkpoint inhibitors. Only six cases (4.4%) had loss of MMR protein expression. There was no significant relationship between MSI status and age (p = 0.496), FIGO stage (p = 0.357), initial treatment (primary debulking surgery [PDS] or neoadjuvant chemotherapy) (p = 0.419), residual tumor after PDS or interval debulking surgery (p = 0.202), and expression of CD8 (p = 0.126), PD-L1 (p = 0.432), and PD-1 (p = 0.653). These results suggest that only a small number of MSI cases in ovarian cancer can be effectively treated with immune checkpoint inhibitor monotherapy. Therefore, to improve the prognosis of ovarian carcinoma, a combination therapy of immune checkpoint inhibitors and other anticancer drugs is necessary.

Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).

Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.

ARID1B as a Potential Therapeutic Target for ARID1A-Mutant Ovarian Clear Cell Carcinoma.

AT-rich interactive domain 1A (ARID1A) and AT-rich interactive domain 1B (ARID1B) are subunits of the SWI/SNF chromatin complex. ARID1A is a tumor suppressor gene that is frequently mutated (46%) in ovarian clear cell carcinomas (OCCC). Loss of ARID1B in an ARID1A-deficient background eliminates the intact SWI/SNF complex, indicating that ARID1B is essential for the formation or stabilization of an intact SWI/SNF complex and, thus, the survival of ARID1A-mutant cancer cell lines. In this study, we investigated the clinicopathologic and prognostic relevance of ARID1B in OCCC by immunohistochemical analysis of 53 OCCC patient samples and loss-of-function experiments in OCCC cell lines. We also examined whether ARID1B could be a therapeutic target or prognostic biomarker in OCCC. siRNA-mediated knockdown of ARID1B in an ARID1A-mutant cell line significantly decreased cell growth, whereas concurrent depletion of both ARID1A and ARID1B was required to decrease wild type cell growth. In the immunohistochemical analyses, low ARID1B level was frequent in samples lacking ARID1A and was associated with shorter progression-free survival. This is the first report demonstrating that a low ARID1B level could be a marker of poor prognosis in OCCC. Moreover, the correlation between the loss of ARID1A immunoreactivity and reduced ARID1B levels indicates that ARID1B could be an attractive target for anti-cancer therapy.

Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report.

Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), MutS Homolog 6 (MSH6), and PMS1 Homolog 2 (PMS2)). The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers.

Association of a single nucleotide polymorphism (rs27434) in the ERAP1 gene with plural tissue weight.

Our study was designed to examine the correlation between single nucleotide polymorphism (SNP) in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene, specifically focusing on rs27434, and plural tissue weight. We conducted this investigation using autopsy samples from the Japanese population. Blood samples were collected from 178 Japanese subjects who had undergone autopsies in Shimane Prefecture. Genomic DNA was subsequently extracted from these samples. SNP (rs27434, G＞A substitution) was analyzed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. In the present study, rs27434 exhibited a statistically significant association with brain weight (g) in both female and male individuals. Among males, rs27434 displayed significant relationships with liver weight (g), and body surface area (m2). In females, rs27434 was significantly related to the length of the appendix. Across both genders, individuals with GA and AA genotypes tended to exhibit higher levels in these respective measurements compared to those with the GG genotype. These results suggest that genetic variant of ERAP1 gene may influence the weight of the organs. To the best of our knowledge, this is the first study investigating the interaction between the association of rs27434 in the ERAP1 gene and data routinely measured at autopsy, such as tissue weight. However, conducting further investigations with larger population samples could provide more comprehensive insights to clarify this issue.

Evaluation of ARID1A as a Potential Biomarker for Predicting Response to Immune Checkpoint Inhibitors in Patients with Endometrial Cancer.

BACKGROUND: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment. METHODS: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis. RESULTS: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage. CONCLUSION: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer.

A call to action: Unpacking the challenges to implementing social sustainability initiatives in a developing country city.

With cities sprawling and populations booming in developing regions, ensuring social sustainability in urban areas has become more urgent. This study investigates the challenges of implementing social sustainability initiatives for cities in developing countries, focusing on Dhaka as a representative city. A mixed-method approach involving structured questionnaire surveys and key informant interviews was used to collect quantitative and qualitative data. The study identified eighteen challenges to implementing social sustainability initiatives in Dhaka city, including a lack of poor urban governance, an inefficient city management system, a lack of political stability, a long delay in the planning approval process, etc. Additionally, experts identified additional challenges that require attention. The study offers empirical evidence to assist government officials, policymakers, and urban planners overcome these challenges and implement social sustainability effectively. To address the identified challenges, the study recommends revisiting the Structure Plan, Urban Area Plan, Detailed Area Plan, and Urban Sector Policy-2011. It highlights the crucial role of community social workers in mitigating specific issues in socially sustainable urban development. Eventually, the study will contribute to the implementation of SDG-11 in the 2030 Agenda for Sustainable Development by bridging the gap between urbanization and socially sustainable cities.