Perinatal dietary patterns and symptomatic depression: A prospective cohort study.

To promote maternal and infant health, there is a need to optimise the dietary pattern of pregnant women to reduce perinatal depression. This prospective cohort study was conducted from June 2020 to February 2022, 300 women from a medical center were interviewed during late pregnancy and at 4-6 weeks postpartum. Dietary patterns were derived by factor analysis using a semiquantitative food frequency questionnaire. Symptomatic depression was defined using the Edinburgh Postpartum Depression Scale (EPDS, ranged 0-30). Their dairy, vegetable and fruit intakes were below the Taiwanese recommendations for pregnant women. Symptomatic depression (EPDS ≥10) affected 31.3% in the third trimester and 35.7% postpartum. Pre- and post-EPDS scores were positively correlated (r = 0.386, p < 0.001). Approximately 55% of those depressed before delivery were also depressed postpartum. For late pregnancy, four dietary patterns were identified ('Good oil', 'Vegetables and fruits', 'Omnivorous' and 'Refined-grain and organ meats'). Dietary patterns were classified according to quartiles (Q). Higher omnivorous pattern scores reduced the risk of depression. For prenatal depression, with Q1 as a reference, the risk was reduced by 38% for Q2, 43% for Q3 and 59% for Q4 (p for trend = 0.068). These findings became evident postpartum (reduced risk by 68% for Q2, 69% for Q3 and 70% for Q4 (p = 0.031; p for trend = 0.0032). The association between dietary patterns and depression encourages the routine nutritional management of pregnant women.

Culture of leukocyte-derived cells from human peripheral blood: Increased expression of pluripotent genes OCT4, NANOG, SOX2, self-renewal gene TERT and plasticity.

There are few stem cells in human peripheral blood (PB). Increasing the population and plasticity of stem cells in PB and applying it to regenerative medicine require suitable culture methods. In this study, leukocyte populations 250 mL of PB were collected using a blood separator before that were cultured in optimal cell culture medium for 4 to 7 days. After culturing, stemness characteristics were analyzed, and red blood cells were removed from the cultured cells. In our results, stemness markers of the leukocyte populations Sca-1+ CD45+, CD117+ CD45+, and very small embryonic-like stem cells CD34+ Lin- CD45- and CXCR4+ Lin- CD45- were significantly increased. Furthermore, the expression of stem cell genes OCT4 (POU5F1), NANOG, SOX2, and the self-renewal gene TERT was analyzed by quantitative real-time polymerase chain reaction in these cells, and it showed a significant increase. These cells could be candidates for multi-potential cells and were further induced using trans-differentiation culture methods. These cells showed multiple differentiation potentials for osteocytes, nerve cells, cardiomyocytes, and hepatocytes. These results indicate that appropriate culture methods can be applied to increase expression of pluripotent genes and plasticity. Leukocytes of human PB can be induced to trans-differentiate into pluripotent potential cells, which will be an important breakthrough in regenerative medicine.

Ganoderma tsugae suppresses the proliferation of endometrial carcinoma cells via Akt signaling pathway.

Ganoderma is one of the common medicinal mushrooms in traditional Chinese medicine. Previous researches have unveiled the multifaceted biological activity of Ganoderma extract. Ganoderma tsugae has been investigated the potential on curing prostate, colon, lung, epidermoid, breast and ovarian cancers, but not including endometrial cancer. Endometrial cancer is a gynecological malignant tumor with serious drug resistance problem in clinical cancer treatment. This study aimed to demonstrate the first study of Ganoderma on treating endometrial cancer. The Ganoderma tsugae ethanol extract (GTEE) could suppress the proliferation of endometrial cancer cells HEC-1-A, KLE, and AN3 CA. GTEE also induced G1/S phase arrest and mitochondria-mediated apoptosis in endometrial cancer cells. Furthermore, the Akt signaling pathway could be suppressed by GTEE. Therefore, our results suggest for the first time that GTEE has the potential to be an adjuvant therapeutic agent in the treatment of endometrial cancer.

Staphylococcal phosphatidylinositol-specific phospholipase C potentiates lung injury via complement sensitisation.

Staphylococcus aureus is frequently isolated from patients with community-acquired pneumonia and acute respiratory distress syndrome (ARDS). ARDS is associated with staphylococcal phosphatidylinositol-specific phospholipase C (PI-PLC); however, the role of PI-PLC in the pathogenesis and progression of ARDS remains unknown. Here, we showed that recombinant staphylococcal PI-PLC possesses enzyme activity that causes shedding of glycosylphosphatidylinositol-anchored CD55 and CD59 from human umbilical vein endothelial cell surfaces and triggers cell lysis via complement activity. Intranasal infection with PI-PLC-positive S. aureus resulted in greater neutrophil infiltration and increased pulmonary oedema compared with a plc-isogenic mutant. Although indistinguishable proinflammatory genes were induced, the wild-type strain activated higher levels of C5a in lung tissue accompanied by elevated albumin instillation and increased lactate dehydrogenase release in bronchoalveolar lavage fluid compared with the plc- mutant. Following treatment with cobra venom factor to deplete complement, the wild-type strain with PI-PLC showed a reduced ability to trigger pulmonary permeability and tissue damage. PI-PLC-positive S. aureus induced the formation of membrane attack complex, mainly on type II pneumocytes, and reduced the level of CD55/CD59, indicating the importance of complement regulation in pulmonary injury. In conclusion, S. aureus PI-PLC sensitised tissue to complement activation leading to more severe tissue damage, increased pulmonary oedema, and ARDS progression.

Proteomic profiling of Ganoderma tsugae ethanol extract-induced adipogenesis displaying browning features.

Ganoderma is classified as a top grade traditional Chinese medicine for promoting human health by regulating 'vital energy'. Its potency towards metabolism and energy homeostasis, particularly, metabolic adaptations of adipocytes, needs to be re-evaluated through an evidence-based study. Here, the triterpenoid-rich Ganoderma tsugae ethanol extract (GTEE) was found to contribute towards adipogenesis accompanied with elevated intracellular lipid metabolic flux. Additionally, proteomic profiling revealed GTEE-upregulated mitochondrial remodeling and chemical energy redox modifications, which display UCP1-positive browning fat-selective features and a NADH-mediated adaptive mechanism. GTEE-treated mice with diet-induced obesity also resulted in the amelioration of white adipocyte hypertrophy and the appearance of UCP1-positive browning adipocytes. Our novel findings unravel that GTEE could promote intracellular metabolic flexibility and plasticity followed by the induction of adipocyte browning.

A rational approach for cancer stem-like cell isolation and characterization using CD44 and prominin-1(CD133) as selection markers.

The availability of adequate cancer stem cells or cancer stem-like cell (CSC) is important in cancer study. From ovarian cancer cell lines, SKOV3 and OVCAR3, we induced peritoneal ascites tumors in immunodeficient mice. Among the cells (SKOV3.PX1 and OVCAR3.PX1) from those tumors, we sorted both CD44 and CD133 positive cells (SKOV3.PX1_133+44+, OVCAR3.PX1_133+44+), which manifest the characteristics of self-renewal, multi-lineage differentiation, chemoresistance and tumorigenicity, those of cancer stem-like cells (CSLC). Intraperitoneal transplantation of these CD44 and CD133 positive cells resulted in poorer survival in the engrafted animals. Clinically, increased CD133 expression was found in moderately and poorly differentiated (grade II and III) ovarian serous cystadenocarcinomas. The ascites tumor cells from human ovarian cancers demonstrated more CD133 and CD44 expressions than those from primary ovarian or metastatic tumors and confer tumorigenicity in immunodeficient mice. Compared to their parental cells, the SKOV3.PX1_133+44+ and OVCAR3.PX1_133+44+ cells uniquely expressed 5 CD markers (CD97, CD104, CD107a, CD121a, and CD125). Among these markers, CD97, CD104, CD107a, and CD121a are significantly more expressed in the CD133+ and CD44+ double positive cells of human ovarian ascites tumor cells (Ascites_133+44+) than those from primary ovarian or metastatic tumors. The cancer stem-like cells were enriched from 3% to more than 70% after this manipulation. This intraperitoneal enrichment of cancer stem-like cells, from ovarian cancer cell lines or primary ovarian tumor, potentially provides an adequate amount of ovarian cancer stem-like cells for the ovarian cancer study and possibly benefits cancer therapy.

Is preoperative bowel preparation necessary for gynecological oncology surgery?

OBJECTIVE: We investigated the necessity of preoperative bowel preparation for gynecological oncology surgery. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection between April 2005 and September 2014 at the Tri-Service General Hospital, Taipei, Taiwan. Patients were divided into two groups based on whether preoperative mechanical bowel preparation (MBP) was performed. Patient characteristics, including duration of antibiotic treatment, surgical procedures, and occurrence of surgical and nonsurgical complications, were compared. RESULTS: We enrolled 124 patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection, of whom 76 received MBP and 48 did not receive mechanical bowel preparation. On comparison between the two groups, no significant differences were noted in the assessed patient characteristics, including mean age (p = 0.61), Federation of Gynecology and Obstetrics stage (p = 0.9), American Society of Anesthesiologists grade (p = 0.9), body mass index (p = 0.8), and residual tumor size (p = 0.86). Furthermore, duration of antibiotic treatment (p = 0.97), surgical procedures (p = 0.99), and total hospital days (p = 0.75), were not different between groups. The risk of surgical (p = 0.78) or nonsurgical (p = 1.0) complications was not significantly higher in the non-MBP group than in the MBP group. CONCLUSION: MBP provides no significant benefit during gynecological oncology surgery. Thus, preoperative MBP is not essential before gynecological oncology surgery and can be omitted.

Ganoderma tsugae Extract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway.

Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT), one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.

Berberine, an isoquinoline alkaloid, inhibits the metastatic potential of breast cancer cells via Akt pathway modulation.

Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanisms by which BBR repressed the metastatic potential of breast cancer cells. BBR was found to downregulate the enzymatic activities and expression levels of matrix metalloproteinases 2 and 9 (MMP2 and MMP9, respectively). The BBR-mediated suppression of MMP2 and MMP9 involved the inhibition of the Akt/nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways. Furthermore, BBR repressed the expression of the Akt protein by modulating the mRNA expression level and protein degradation of Akt. In conclusion, this study suggests that BBR can reduce the metastatic potential of highly metastatic breast cancer cells and may be a useful adjuvant therapeutic agent in the treatment of breast cancer by targeting the Akt pathway.

Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB.

Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- and time-dependent manner. Transrepression of HER2 promoter activity by TPL is also observed. The interacting site of TPL on the HER2 promoter region is located between -207 and -103 bps, which includes a putative binding site for the transcription factor NF-κB. Previous reports demonstrated that TPL suppresses NF-κB expression. We demonstrate that overexpression of NF-κB rescues TPL-mediated suppression of HER2 promoter activity and protein expression in NIH3T3 cells and ovarian cancer cells, respectively. In addition, TPL downregulates the activated (phosphorylated) forms of HER2, phosphoinositide-3 kinase (PI3K), and serine/threonine-specific protein kinase (Akt). TPL also inhibits tumor growth in a mouse model. Furthermore, TPL suppresses HER2 and Ki-67 expression in xenografted tumors based on an immunohistochemistry (IHC) assay. These findings suggest that TPL transrepresses HER2 and suppresses the downstream PI3K/Akt-signaling pathway. Our study reveals that TPL can inhibit tumor growth and thereby may serve as a potential chemotherapeutic agent.

Functional characterization of transmembrane intracellular pH regulators and mechanism of alcohol-induced intracellular acidosis in human umbilical cord blood stem cell-like cells.

Changing intracellular pH (pHi) exerts considerable influence on many cellular functions. Different pHi regulators, such as the Na-H exchanger (NHE), Na/(Equation is included in full-text article.)symporter, and Cl/OH exchanger (CHE), have been identified in mature mammalian cells. The aims of the present study were to investigate the physiological mechanisms of pHi recovery and to further explore the effects of alcohol on the pHi in human umbilical cord blood CD34 stem cell-like cells (HUCB-CD34STs). HUCB-CD34STs were loaded with the pH-sensitive dye, 2',7'-bis(2-carboxethyl)-5(6)-carboxyfluorescein, to examine pHi. In isolated HUCB-CD34STs, we found that (1) the resting pHi is 7.03 ± 0.02; (2) 2 Na-dependent acid extruders and a Cl-dependent acid loading carrier exist and are functional; (3) alcohol functions in a concentration-dependent manner to reduce pHi and increase NHE activity, but it does not affect CHE activity; and (4) fomepizole, a specific alcohol dehydrogenase inhibitor, does not change the intracellular acidosis and NHE activity-induced by alcohol, whereas 3-amino-1, 2,4-trizole, a specific catalase inhibitor, entirely abolishes these effects. In conclusion, we demonstrate that 2 acid extruders and 1 acid loader (most likely NHE, NBC, and CHE, respectively) functionally existed in HUCB-CD34STs. Additionally, the intracellular acidosis is mainly caused by catalase-mediated alcohol metabolites, which provoke the activity of NHE.

Lentiviral short hairpin RNA screen of human kinases and phosphatases to identify potential biomarkers in oral squamous cancer cells.

Oral carcinoma is a serious public health problem and the leading cause of head and neck cancer mortality worldwide. Moreover, oral cancer patients often present symptoms at a late stage and show a high recurrence rate after treatment. Therefore, there is an urgent need to identify novel biomarkers for early diagnosis or clinical oral cancer therapy. In this study, we employed a subset of lentiviral short hairpin RNAs targeted against various kinases and phosphatases, designed by The RNAi Consortium, to screen systemically and in a high-throughput manner for potential growth regulators of oral cancer cells. The screen revealed a total of 50 candidate genes, for which more than 90% of growth inhibition in human oral squamous cancer HSC-3 cells was obtained. Furthermore, bioinformatic analysis of these candidate genes identified transforming growth factor-ß receptor type II- and fms-related tyrosine kinase 3-related molecular pathways that are involved in NF-κB-mediated growth of HSC-3 cells. These candidate genes may be potential biomarkers for early diagnosis of oral cancer. In addition, these candidate genes represent potential targets for anticancer drug design helping to develop a personalized treatment to combat oral cancer.

Growth suppression of HER2-overexpressing breast cancer cells by berberine via modulation of the HER2/PI3K/Akt signaling pathway.

Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. This study investigated the molecular mechanisms by which BBR suppresses the growth of HER2-overexpressing breast cancer cells. The results show that BBR induces G1-phase cell cycle arrest by interfering with the expression of cyclins D1 and E and that it induces cellular apoptosis through the induction of a mitochondria/caspase pathway. The data also indicate that BBR inhibits cellular growth and promotes apoptosis by down-regulating the HER2/PI3K/Akt signaling pathway. Furthermore, it is also shown that a combination of taxol and BBR significantly slows the growth rate of HER2-overexpressing breast cancer cells. In conclusion, this study suggests that BBR could be a useful adjuvant therapeutic agent in the treatment of HER2-overexpressing breast cancer.

Evaluating the effects of immunosuppression by in-vivo bioluminescence imaging after allotransplantation of ovarian grafts.

Bioluminescence imaging (BLI) has been introduced for studies of ongoing biological processes but has never been applied for ovarian transplantation. Here, BLI was used as a novel approach to trace the survival of ovarian grafts. The ovarian donors were transgenic mice carrying FVB/N-Tg (PolII-luc) as a reporter gene, encoding luciferase to catalyse luciferin which results in visible light emission as bioluminescence. There were three groups of recipients: (i) group A: BALB/c mice without immunosuppressant treatment; (ii) group B: BALB/c mice receiving a cocktail immunosuppressant treatment; and (iii) group C: immunodeficient NOD-SCID mice without immunosuppression. Luciferin BLI was used to follow graft survival, and viable follicle numbers were counted as a measure of success. Bioluminescence intensity fluctuated but was consistent with the end-point counts of viable follicle numbers. Group A showed loss of viable follicles and bioluminescence disappeared as early as day 10 following ovarian engraftment, indicating strong immune rejection. Groups B and C showed graft survival and measurable bioluminescence for up to 30 days. In conclusion, BLI provided non-invasive longitudinal dynamic monitoring of ovarian grafts with excellent sensitivity and spatial resolution. This approach should prove valuable for research on ovarian transplantation.

Tubal ligation via colpotomy or laparoscopy: a retrospective comparative study.

OBJECTIVE: To compare transvaginal with laparoscopic tubal sterilization with respect to invasiveness and outcomes. METHOD: The outcomes of 103 patients who received interval tubal sterilization were compared. Group A (n = 38) underwent the transvaginal approach, group B (n = 38) a laparoscopic approach, and group C (n = 27) underwent mini-laparotomy due to difficulties encountered in one of the other procedures. RESULTS: There were no significant differences in patient age between the groups. There was no significant difference in operative time or blood loss between groups A and B. Operative time was significantly longer in group C (120 ± 35 min) than group A (40 ± 5 min) or group B (45 ± 9 min) (p < 0.05). Blood loss was significantly greater in group C (120 ± 30 ml) than in group A (10 ± 2 ml) or group B (10 ± 1 ml) (p < 0.05). The cost of transvaginal tubal sterilization was the lowest, and that of mini-laparotomy was the highest. There was no contraception failure in any group. CONCLUSIONS: Transvaginal tubal sterilization is technically more difficult, but when correctly performed it is not associated with an increased complication rate, and is less costly than laparoscopic sterilization.

Tracking the rejection and survival of mouse ovarian iso- and allografts in vivo with bioluminescent imaging.

The applications of in vivo bioluminescent imaging (BLI) with a luciferase reporter gene occur widely across biomedical fields. Luciferase-transgenic mice are highly useful donors for tracking transplanted ovarian tissues. Realizing the full potential of this system may greatly benefit the study of the physiological behaviour and function of transplanted grafts, and the rapid and reliable evaluation of new transplantation protocols. The ovarian tissues of donor FVB/N-Tg(PolII-Luc)Ltc transgenic mice, with a luciferase transgene as the reporter, were transplanted into iso/allogeneic recipients. Rejection, ovarian function and BLI were quantitatively analysed in vivo over time. The BLI of the ovarian isografts revealed longer survival than that of allografts, even with cyclosporine A (CsA) treatment. The CD4(+)/CD8(+) ratios of peripheral T-cells were significantly reduced in allografts compared with those in isografts (P<0.0001) during rejection, whereas CD19(+) cell numbers were higher in allografts. The infiltration of CD4(+)/CD8(+) cells into the graft was unremarkable in isografts from day 1, but was strong in allografts from day 8 onwards. Hormone activity revealed complete oestrus cycles in the isografts but only the dioestrus stage in the allografts. These results demonstrate that BLI in vivo expedites the fast throughput and fate maps of ovarian grafts. The use of BLI to longitudinally monitor ovarian grafts for immunorejection demonstrated the short survival of allografts and the much longer survival of isografts. CsA treatment alone is ineffective against the acute rejection of ovarian allografts.

Protective effect of a gonadotropin-releasing hormone analogue on chemotherapeutic agent-induced ovarian gonadotoxicity: a mouse model.

OBJECTIVE: To demonstrate the protective effect of triptorelin, a GnRH analogue, on chemotherapy-induced ovarian gonadotoxicity. STUDY DESIGN: Twenty-four sexually mature, virgin, female FVB/NJNarl mice were divided into four groups: busulfan (B); low-dose triptorelin plus busulfan (T(L)+B); high-dose triptorelin plus busulfan (T(H)+B); and control. Mice in the T(L)+B and T(H)+B groups were injected with 3.8 and 38 mg/kg of triptorelin subcutaneously, respectively. Four weeks later, mice in the B, T(L)+B, and T(H)+B groups were injected with busulfan intraperitoneally at a dose of 36 mg/kg. Histologic examinations were performed 4 weeks later. RESULTS: Obvious destruction of ovarian structure and significant depletion of primordial, primary, and secondary follicles were demonstrated in the B group compared with the control group, affirming the gonadotoxicity of busulfan. In the T(L)+B group, a greater number of larger primordial and primary follicles were enumerated compared with the B group; however, statistical significance was not achieved. In the T(H)+B group, the number of primordial and primary follicles was significantly greater than in the B group, and the ovarian tissue in the T(H)+B group was spared, demonstrating the effect of triptorelin pre-treatment on ovarian protection. CONCLUSION: Our results have demonstrated a dose-dependent protective effect against gonadotoxic chemotherapy of a GnRH analogue on ovarian reserve, thus suggesting a novel application of GnRH analogues in fertility preservation.