Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos.

BACKGROUND: In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. METHODS: We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on days or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for aneuploidy prediction and consequent live-birth outcomes. RESULTS: These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709-0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. CONCLUSIONS: Our study underscores the AI model's ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Human Umbilical Cord Mesenchymal Stem Cells Derived Exosomes Improved The Aged Mouse IVM Oocytes Quality.

During assisted reproductive technology (ART) treatment, the aged women, especially those over 35 years old, have fewer mature oocytes and poorer quality of the oocytes comparing with the young women. In vitro maturation (IVM) technology facilitates the usage of immature oocytes, which is clinically important for the aged women. However, the maturation rate is low for the oocytes from the aged women. Human umbilical cord mesenchymal stem cells derived exosomes (HUCMSCs-exosomes), as important mediators of intercellular communication, have been widely used to restore ovarian function and improve female fertility. In this study, we isolated HUCMSCs-exosomes and collected the immature germinal vesicle oocytes from the naturally aged mouse model. And we added these HUCMSCs-exosomes to the conventional IVM culture system. The effects of HUCMSCs-exosomes on IVM oocytes were observed and analyzed from multiple aspects including maturation rate, spindle morphology, mitochondria function, and development potential. We found the quality of oocytes was improved by HUCMSCs-exosomes. Based on the results, we propose that HUCMSCs-exosomes may provide a novel and cell free strategy in the improvement of the IVM in elderly infertile women in the future.

Electronic Interactive Games for Glycemic Control in Individuals With Diabetes: Systematic Review and Meta-Analysis.

BACKGROUND: Several electronic interventions have been used to improve glycemic control in patients with diabetes. Electronic interactive games specific to physical activity are available, but it is unclear if these are effective at improving glycemic control in patients with diabetes. OBJECTIVE: This study aimed to determine the effects of electronic game-based interventions on glycemic control in patients with diabetes. METHODS: Relevant studies that were published before April 1, 2023, were searched from 5 databases: PubMed, Embase, Web of Science, Scopus, and Cochrane Library. Eligibility criteria included prospective studies examining the relationship between electronic games with physical activities or diet education and glycemic control as the outcome. The risk of bias was assessed using the Cochrane risk-of-bias tool. All analyses were conducted using RevMan5.4.1. Depending on the heterogeneity across studies, the pooled effects were calculated using fixed-effects or random-effects models. RESULTS: Participants from 9 studies were included and assessed. Glycated hemoglobin (HbA1c) and fasting blood glucose improved in the intervention group, although the analysis revealed no significant reduction in HbA1c (-0.09%, 95% CI -0.29% to 0.10%) or fasting blood glucose (-0.94 mg/dL, 95% CI -9.34 to 7.46 mg/dL). However, the physical activity of individuals in the intervention group was significantly higher than that of those in the control group (standardized mean difference=0.84, 95% CI 0.30 to 1.38; P=.002). Other outcomes, such as weight and blood lipids, exhibited no significant improvement (all P>.05). CONCLUSIONS: Electronic games had a good impact on participants' physical activity and offered an advantage in glycemic control without reaching statistical significance. Electronic games are convenient for reminders and education. Low-intensity exercise games may not be considered a better adjuvant intervention to improve diabetes self-management care.

Citrullinated fibrinogen-SAAs complex causes vascular metastagenesis.

Primary tumor cells metastasize to a distant preferred organ. However, the most decisive host factors that determine the precise locations of metastases in cancer patients remain unknown. We have demonstrated that post-translational citrullination of fibrinogen creates a metastatic niche in the vulnerable spots. Pulmonary endothelial cells mediate the citrullination of fibrinogen, changing its conformation, surface charge, and binding properties with serum amyloid A proteins (SAAs), to make it a host tissue-derived metastatic pathogen. The human-specific SAAs-citrullinated fibrinogen (CitFbg) complex recruits cancer cells to form a protein-metastatic cell aggregation in humanized SAA cluster mice. Furthermore, a CitFbg peptide works as a competitive inhibitor to block the homing of metastatic cells into the SAAs-CitFbg sites. The potential metastatic sites in the lungs of patients are clearly visualized by our specific antibody for CitFbg. Thus, CitFbg deposition displays metastatic risks for cancer patients, and the citrullinated peptide is a new type of metastasis inhibitor.

Advances in natural products and antibody drugs for SLE: new therapeutic ideas.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune systemic disease with a wide range of clinical symptoms, complex development processes, and uncertain prognosis. The clinical treatment of SLE is mainly based on hormones and immunosuppressants. Research on novel therapy strategies for SLE has flourished in recent years, especially the emergence of new targeted drugs and natural products that can modulate related symptoms. This review discusses the current experience including B-cell targeted drugs (belimumab, tabalumab, blisibimod, atacicept, rituximab, ofatumumab, ocrelizumab, obexelimab, and epratuzumab), T-cell targeted drugs (abatacept, dapirolizumab, and inhibitor of syk and CaMKIV), cytokines targeted drugs (anifrolumab and sifalimumab), and natural products (curcumin, oleuropein, punicalagin, sulforaphane, icariin, apigenin, and resveratrol). The aim of this paper is to combine the existing in vitro and in vivo models and clinical research results to summarize the efficacy and mechanism of natural drugs and targeted drugs in SLE for the reference and consideration of researchers.

Preimplantation genetic testing for aneuploidy helps to achieve a live birth with fewer transfer cycles for the blastocyst FET patients with unexplained recurrent implantation failure.

PURPOSE: This retrospective cohort study aimed to investigate the value of preimplantation genetic testing for aneuploidy (PGT-A) as a screening test for patients suffering from unexplained recurrent implantation failure (RIF). METHODS: After screening patients in one reproductive medicine center, twenty-nine, forty-nine and thirty-eight women (< 40 years old) who had suffered unexplained RIF with PGT-A, or RIF without PGT-A, or no RIF with PGT-A were included. The clinical pregnancy rate and live birth rate per transfer, the conservative and optimal cumulative clinical pregnancy rates (CCPR) and live birth rates (CLBR) after three blastocyst FETs were analyzed. RESULTS: The live birth rate per transfer was significantly higher in the RIF + PGT-A group than that in the RIF + NO PGT-A group (47.6% vs. 24.6%, p = 0.014). After 3 cycles of FET, RIF + PGT-A group had significantly higher conservative CLBR and optimal CLBR compared to the RIF + NO PGT-A group (69.0% vs. 32.7%, p = 0.002 and 73.7% vs. 57.5%, p = 0.016), but had similar conservative and optimal CLBRs compared to the NO RIF + PGT-A group. The number of FET cycles required when half women achieved a live birth was 1 in the PGT-A group and 3 in RIF + NO PGT-A group. The miscarriage rates were not different between the RIF + PGT-A and RIF + NO PGT-A, RIF + PGT-A and NO RIF + PGT-A groups. CONCLUSION: PGT-A did be superior in reducing the number of transfer cycles required to achieve a similar live birth rate. Further studies to identify the RIF patients who would benefit most from PGT-A are necessary.

Suppression of CEBPδ recovers exhaustion in anti-metastatic immune cells.

The pre-metastatic microenvironment consists of pro-metastatic and anti-metastatic immune cells in the early stages of cancer, when the primary tumor begins to proliferate. Redundantly, pro-inflammatory immune cells predominated during tumor growth. Although it is well known that pre-metastatic innate immune cells and immune cells fighting primary tumor cells become exhausted, the mechanism by which this occurs is unknown. We discovered that anti-metastatic NK cells were mobilized from the liver to the lung during primary tumor progression and that the transcription factor CEBPδ, which was upregulated in a tumor-stimulated liver environment, inhibited NK cell attachment to the fibrinogen-rich bed in pulmonary vessels and sensitization to the environmental mRNA activator. CEBPδ-siRNA treated anti-metastatic NK cells regenerated the binding proteins that support sitting in fibrinogen-rich soil, such as vitronectin and thrombospondin, increasing fibrinogen attachment. Furthermore, CEBPδ knockdown restored an RNA-binding protein, ZC3H12D, which captured extracellular mRNA to increase tumoricidal activity. Refreshed NK cells using CEBPδ-siRNA with anti-metastatic abilities would work at metastatic risk areas in the pre-metastatic phase, resulting in a reduction in lung metastasis. Furthermore, tissue-specific siRNA-based therapy in lymphocyte exhaustion may be beneficial in the treatment of early metastases.

Presence of periodontitis may synergistically contribute to cancer progression via Treg and IL-6.

A close causal relationship has been suggested to exist between cancer and periodontitis. We hypothesized that the immune surveillance system is impaired in patients with periodontitis, which contributes to cancer development and growth. Therefore, the present study investigated the relationship between immune surveillance mechanisms and periodontitis in cancer patients. The presence or absence of periodontitis was assessed and the peripheral blood (PB) concentrations of IL-6, immunosuppressive cytokines (VEGF, TGF-ß1, and CCL22) and proportion of T regulatory cells (Treg, CD3 + CD4 + CD25 + Foxp3 +) were measured. Subjects were classified into the following four groups: non-cancer patients without periodontitis (C - P -), non-cancer patients with periodontitis (C - P +), cancer patients without periodontitis (C + P -), and cancer patients with periodontitis (C + P +). The results of a multivariate analysis showed that the PB concentration of IL-6 was significantly higher in C + than in C- and higher in C + P + than in C + P -. The PB proportion of Treg was significantly higher in C + P + than in C + P -, C - P + , and C - P -. The results of this study suggested that the presence of periodontitis and cancer synergistically increased Treg in PB, which may be one of the underlying causes of immunosuppression and immune evasion in cancer. It was also suggested that the presence of periodontal disease and/or cancer also increases IL-6 in PB, which would be associated with cancer progression. These results suggest the possibility that the presence of periodontitis might synergistically contribute to cancer progression.

Clinical analysis of total endoscopic thyroidectomy via breast areola approach in early differentiated thyroid cancer.

PURPOSE: The purpose of this study was to explore the efficacy and safety of total endoscopic thyroidectomy (TET) via breast areola approach in the treatment of early differentiated thyroid cancer. METHODS: The clinical data of 134 patients with early differentiated thyroid cancer were retrospectively analyzed. The patients underwent different treatments, including TET via breast areola approach in endoscope group (n=67), and conventional small incision open surgery in control group (n=67). The surgery-related indexes, complications, postoperative incision recovery, visual analogue scale (VAS) pain score, postoperative patients' satisfaction, tumor recurrence and survival conditions were compared between the two groups. RESULTS: Compared with control group, the endoscope group showed significantly longer operation time, smaller intraoperative bleeding, less postoperative drainage, shorter duration of postoperative catheter indwelling and shorter postoperative length of stay. Meanwhile, in the endoscope group, the postoperative VAS pain score was markedly lower than that in control group, and the postoperative patients' satisfaction was higher than that in control group. The neurological severity score (NSS) had statistically significant differences between the two groups at 3 months and 6 months after operation. Moreover, no tumor recurrence and metastasis were found during the follow-up period. CONCLUSIONS: TET via breast areola approach is safe and effective in the treatment of early differentiated thyroid cancer, and it can achieve a better cosmetic effect and high satisfaction of patients, which is worthy of clinical application.

Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway.

As a newly approved oral hypoglycaemic agent, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, which is derived from the natural product phlorizin can effectively reduce blood glucose. Recent clinical studies have found that dapagliflozin alleviates non-alcoholic fatty liver disease (NAFLD), but the specific mechanism remains to be explored. This study aimed to investigate the underlying mechanism of dapagliflozin in alleviating hepatocyte steatosis in vitro and in vivo. We fed the spontaneous type 2 diabetes mellitus rats with high-fat diets and cultured human normal liver LO2 cells and human hepatocellular carcinoma HepG2 cells with palmitic acid (PA) to induce hepatocellular steatosis. Dapagliflozin attenuated hepatic lipid accumulation both in vitro and in vivo. In Zucker diabetic fatty (ZDF) rats, dapagliflozin reduced hepatic lipid accumulation via promoting phosphorylation of acetyl-CoA carboxylase 1 (ACC1), and upregulating lipid ß-oxidation enzyme acyl-CoA oxidase 1 (ACOX1). Furthermore, dapagliflozin increased the expression of the autophagy-related markers LC3B and Beclin1, in parallel with a drop in p62 level. Similar effects were observed in PA-stimulated LO2 cells and HepG2 cells. Dapagliflozin treatment could also significantly activated AMPK and reduced the phosphorylation of mTOR in ZDF rats and PA-stimulated LO2 cells and HepG2 cells. We demonstrated that dapagliflozin ameliorates hepatic steatosis by decreasing lipogenic enzyme, while inducing fatty acid oxidation enzyme and autophagy, which could be associated with AMPK activation. Moreover, our results indicate that dapagliflozin induces autophagy via the AMPK-mTOR pathway. These findings reveal a novel clinical application and functional mechanism of dapagliflozin in the treatment of NAFLD.

Effect of Acid or Base Interventions on Bone Health: A Systematic Review, Meta-Analysis, and Meta-Regression.

Osteoporosis is a global health issue among the aging population. The effect of the acid or base interventions on bone health remains controversial. This study performed a systematic review and meta-analysis to investigate effects of acidic diets and alkaline supplements on bone health simultaneously. We conducted a comprehensive literature search in 5 available databases and 1 registered clinical trial system to identify randomized controlled trials (RCTs) that assessed effects of the acid-base intervention on bone health. Depending on heterogeneity across studies, the pooled effects were calculated by fixed-effects or random-effects models. The present study included 13 acidic diet intervention studies and 13 alkaline supplement studies for final quantitative assessments. The meta-analysis showed that acidic diets significantly increased net acid excretion [NAE; standardized mean difference (SMD) = 2.99; P = 0.003] and urinary calcium excretion (SMD = 0.47, P < 0.00001) but had no significant effect on bone turnover markers and bone mineral density (BMD). On the other hand, alkaline supplement intervention significantly reduced NAE (SMD = -1.29, P < 0.00001), urinary calcium excretion (SMD = -0.44, P = 0.007), bone resorption marker aminoterminal cross-linking telopeptide (NTX; SMD = -0.29, P = 0.003), and bone formation marker osteocalcin (OC; SMD = -0.23, P = 0.02), but did not affect the other bone turnover markers. Furthermore, alkaline supplements significantly increased BMD in femoral neck [mean difference (MD) = 1.62, P < 0.00001, I2 = 0%], lumbar spine (MD = 1.66, P < 0.00001, I2 = 87%), and total hip (MD = 0.98, P = 0.02, I2 = 99%). Subsequently, meta-regression analyses identified 1 study that substantially contributed to the high heterogeneity of BMD in the latter 2 sites, but sensitivity analysis suggested that this study did not affect the significant pooled effects. Despite that, the results should be interpreted with caution and need to be further validated by a larger RCT. In summary, through integrating evidence from RCTs, the present meta-analysis initially suggests that alkaline supplements may be beneficial to bone metabolism and acidic diets may not be harmful to bone health. This work may be clinically useful for both clinicians and patients with osteoporosis.

Effects of COH on the expression of connexin43 in endometrial stromal cells.

OBJECTIVE: The purpose of this study was to investigate the effect of controlled ovarian hyperstimulation (COH) on gap junction, and to induce the effect of an estrogen level overdose on gap junction in vitro by COH. Here, we mainly focus on connexion43 (Cx43), progesterone receptor (PR) and prolactin-related protein (PRP), and CyclinD3 genes expression, as well as the expression of Cx43 protein, were investigated. MATERIALS AND METHODS: Mature BDF-1 mice were divided into different COH, and the mouse uterus was isolated, Paraffin sections evaluate the effect of COH on mouse uterine endometrial morphology. The other part was used for the extraction of mouse uterine endometrial stromal cells (ESC), some related gene changes are detected. Human ESC were isolated from human endometrium by primary culture, the estrogen concentrations 10-6 mol/L, 10-7 mol/L were added, the changes of Cx43 gene and related proteins were detected, too. RESULTS: (1) HE staining showed that in the ovulatory endometrium of mice in the high super ovulation group, uterine glands in the stromal layer were significantly increased, the relative vascular tissues was less abundant. (2) In three groups of COH mice, the expression of Cx43, PR, and PRP genes in ESC was significantly different (P < 0.05). (3) In vitro ESC in the COH group showed significant differences in Cx43, PR, and CyclinD3 gene expression (P < 0.05), and showed an obvious dose effect. In addition, Western blot analysis showed that the Cx43 protein and Cx43 gene expression were similar. CONCLUSIONS: (1) Animal experiments study showed that Cx43 gene expression in ESC was significantly decreased in hyper COH, in addition, the advance in gene expression was significantly earlier, suggesting decidualization appeared significantly earlier. (2) In vitro COH demonstrated when the estrogen concentration used was higher, the expression level of Cx43 gene and protein was lower. Combined with animal experiments, the endometrium decidualization was advanced in mice that were underwent hyper COH, which may reflect the endometrial receptivity.

Effects of interleukin 6 and tumor necrosis factor-α on the proliferation of porcine theca interna cells: Possible role of these cytokines in the pathogenesis of polycystic ovary syndrome.

OBJECTIVE: We studied the effects of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) on the proliferation of porcine theca interna (TI) cells and further elucidated the roles of IL-6 and TNF-α in the pathogenesis of polycystic ovary syndrome. MATERIALS AND METHODS: TI cells were treated with 10 pg/mL, 100 pg/mL, and 1000 pg/mL IL-6 or TNF-α. TI cell proliferation was then examined by carboxyfluorescein diacetate succinimidyl ester labeling and flow cytometry. RESULTS: Cell proliferation was not significantly different in TI cells cultured in medium alone (control) or in the presence of IL-6. At 72 hours of treatment, the mean fluorescence intensity was significantly lower in TI cells treated with 100 pg/mL and 1000 pg/mL TNF-α than in the control (p < 0.05). CONCLUSION: TNF-α, but not IL-6, was able to promote TI cell proliferation. Our results suggest that TNF-α might play a role in hyperandrogenism, cortex thickness, and the increased ovary volume observed in polycystic ovaries.

RA induces differentiation of multipotent P19 cells towards male germ cell.

Generating male germ cells in vitro from multipotent stem cells is still a challenge for stem cell biologists. The difficulty is caused by the lack of knowledge about spermatogenesis molecular-controlling mechanisms. In vivo, PGCs differentiate into male germ cells in a very complicated environment through many middle steps. In this study, we use the pluripotent p19 cells to test their responses to different retinoic acid (RA) concentrations by evaluating markers for stem cells (bmp4, egr3), primordial germ cells (ddx4), spermatogonia (c-kit), premeiotic cells (stra8), and male germ cells (dazl and plzf). We have found that cyp26b1, which will catalyze RA, increases dramatically in p19 cells 1 d after RA treatment. Bmp3, egr3, and stra8 are stimulated after 1 d of RA treatment and then recover to normal after 3 d of RA treatment. C-kit keeps being expressed when treated with 10 nM-4 µM RA. Dazl and plzf are gained after 3 d of stimulation. The morphology of RA (100 nM-4 µM)-treated cells changes distinctively, and cell colonies are formed. Typical neural cell-like and germ cell-like morphologies appear in the 100 nM and 4 µM RA groups, respectively. We conclude that 100-500 nM RA can cause responses in p19 cells, but a high concentration of RA (1-4 µM) can drive these pluripotent cells' differentiation towards male germ cells. However, high concentrations of RA are also toxic. Some colonies that survived from 4 µM RA begin to express ddx4 and c-kit. Selection of the c-kit(+), dazl(+), and ddx4(+) cells after RA stimulation and creating a special culture medium for their propagation might benefit successful spermatogenesis induction in vitro.

[Progesterone induction keeps a balanced mitochondrial activity and a low ROS productivity in human sperm].

OBJECTIVE: To observe the relative activity of sperm mitochondria and the proportion of ROS-positive sperm before and after capacitation and progesterone (Pg)-induced hyperactivation, and investigate the functional characteristics of sperm mitochondria. METHODS: We collected 20 samples of normal human spermatozoa that met the criteria of WHO Laboratory Manual for the Examination and Processing of Human Semen (5th ed) and cultured them with the swim-up method in a CO2 incubator at 37 degrees C for 1 hour. We divided the sperm into a pre-capacitation and a capacitated group, and further incubated the capacitated sperm in an upright tube with (Pg-induced group) or without (control group) slow-releasing Pg at 37 degrees C for another hour. Then we determined the relative activity of mitochondria and the percentage of ROS-positive cells in the sperm samples using JC-1 and DCF staining. RESULTS: The relative activities of mitochondria were significantly increased in the capacitated, control and Pg-induced groups (6.23, 14.36 and 12.33) as compared with the pre-capacitation group (1.42) (P < 0.05), while the percentages of balanced mitochondria (mitochondria with equal amount of high and low electric potentials) remarkably reduced (4.27%, 5.03% and 8.57% vs 21.64%, P < 0.05). The percentages of ROS-positive sperm in the pre-capacitation, capacitated, control and Pg-induced groups were 2.89%, 0.70%, 4.25% and 1.90%, respectively, significantly lower in the capacitated than in the pre-capacitation group (P < 0.01), but dramatically increased in the control group after another hour of swim-up incubation and markedly higher than in the Pg-induced group (P < 0.01). CONCLUSION: Progesterone induction can hyperactive human sperm motility, inhibit the relative activity of mitochondria, keep mitochondria potential at a more balanced level, and reduce the production of ROS, which may help to raise the rate of in vitro fertilization and improve the quality of embryos.

c-kit expression profile and regulatory factors during spermatogonial stem cell differentiation.

BACKGROUND: It has been proven that c-kit is crucial for proliferation, migration, survival and maturation of spermatogenic cells. A periodic expression of c-kit is observed from primordial germ cells (PGCs) to spermatogenetic stem cells (SSCs), However, the expression profile of c-kit during the entire spermatogenesis process is still unclear. This study aims to reveal and compare c-kit expression profiles in the SSCs before and after the anticipated differentiation, as well as to examine its relationship with retinoic acid (RA) stimulation. RESULTS: We have found that there are more than 4 transcripts of c-kit expressed in the cell lines and in the testes. The transcripts can be divided into short and long categories. The long transcripts include the full-length canonical c-kit transcript and the 3' end short transcript. Short transcripts include the 3.4 kb short transcript and several truncated transcripts (1.9-3.2 kb). In addition, the 3.4 kb transcript (starting from intron 9 and covering exons 10 ~ 21) is discovered to be specifically expressed in the spermatogonia. The extracellular domain of Kit is obtained in the spermatogonia stage, but the intracellular domain (50 kDa) is constantly expressed in both SSCs and spermatogonia. The c-kit expression profiles in the testis and the spermatogonial stem cell lines vary after RA stimulation. The wave-like changes of the quantitative expression pattern of c-kit (increase initially and decrease afterwards) during the induction process are similar to that of the in vivo male germ cell development process. CONCLUSIONS: There are dynamic transcription and translation changes of c-kit before and after SSCs' anticipated differentiation and most importantly, RA is a significant upstream regulatory factor for c-kit expression.

Reprogrammed peripheral blood mononuclear cells are able to survive longer in irradiated female mice.

Induced multipotent stem (iMS) cells are originated from somatic cells and become multipotent by genetic and/or epigenetic modifications. Previous studies have shown that the fish oocytes extracts (FOE) can induce skin fibroblast cells into iMS cells. In this study, we aim to determine whether FOE can similarly induce mouse peripheral blood mononuclear cells (PBMCs) into the iMS state and if so, whether they can survive longer when they are transplanted into the irradiation female mice. PBMCs of GFP-transgenic male mice were cultured and transiently reprogrammed by FOE. They were deemed reaching the iMS state after detection of expression of stem cell markers. The iMS-like PBMCs were transplanted into female C57BL mice by tail vein injection. The spleen wet weights as well as numbers of colonies of the recipient mice were examined. The results showed the spleen wet weights and numbers of spleen colonies of FOE-induced group were all significantly higher than those of the non-induced group and negative control group. On day 90 after transplantation, FISH analysis detected the presence of Y chromosome in the induced group, but not of the other groups. The current findings demonstrate that FOE-induced PBMCs are able to survive longer in irradiated female mice.

Comparative study among three different methods of bone marrow mesenchymal stem cell transplantation following cerebral infarction in rats.

The objective of this study was to investigate the effects of transplanted bone marrow mesenchymal stem cells (BMSCs) administered via internal jugular vein injection, carotid artery injection, or intraventricular transplantation for the treatment of cerebral infarction, which was modeled in rats. The neurological scores of the treated rats and the distribution of the transplanted cells (GFP-labeled) in the infarction area were evaluated. The cerebral infarction model was produced by inserting a modified Zea-longa suture, which generated middle cerebral artery occlusion (MCAO). The GFP-labeled BMSCs were transplanted through the jugular vein or the carotid artery or by stereotactic intraventricular delivery to the infarction models 1 week after the cerebral infarction was established. The 'Nerve Function Score' of the model rats was recorded before and after BMSC transplantation. Brain tissue sections were examined under a fluorescence microscope. We determined that the transplanted BMSCs rescued brain function, which was indicated by a decrease in the neurological scores (P<0·05) following BMSC transplantation. The effect of BMSC transplantation was reflected in decreases in the neurological score in the intraventricular transplantation group, the carotid artery transplantation group, and the jugular vein graft group*. The transplanted BMSCs were able to migrate to the brain injury area and the cortex and survived the infarction; thus, BMSCs may promote the recovery of nerve function.

Down-regulation of HLA-G Attenuates Cleavage Rate in Human Triploid Embryos.

INTRODUCTION: HLA-G is a major histocompatibility complex (MHC), class Ib molecule that is selectively expressed at the fetal-maternal interface. It is thought to play a role in protecting the fetus from the maternal immune response. Interestingly, the preimplantation embryo development (Ped) gene product Qa-2 is also a mouse MHC class Ib protein that affects cleavage and division of preimplantation mouse embryos and subsequent embryonic survival. Data from many human in vitro fertilization (IVF) clinics suggest that the mouse Ped phenomenon also exists in human because embryos fertilized at the same time have different cleavage rates and consequently different IVF outcomes. As HLA-G is expressed in human early embryos, it is highly regarded as the functional homologue of Qa-2. Whether HLA-G expression is correlated with the cleavage rate of human embryos has great potential clinical value. METHODS: In this study, 45 human early abnormal fertilized embryos (3 PN) from patients undergoing in vitro fertilization were used to test the effects of HLA-G knock-down via infection with adenovirus carrying its specific siRNA on the cleavage rate in a 2-day culture period. One-way ANOVA, Post hoc and Chi-square were used to compare groups. A p-value smaller than 0.05 was considered statistically significant. RESULTS: Knocking-down HLA-G in human pre-implantation stage embryos resulted in a higher cell arrest rate and a slower cleavage rate. CONCLUSION: The results from the present study suggested that HLA-G might play an important role in early human embryo development.

c-kit and its related genes in spermatogonial differentiation.

Spermatogenesis is the process of production of male gametes from SSCs. The SSCs are the stem cells that differentiate into male gametes in the testis. in the mean time, the Spg are remarkable for their potential multiple trans-differentiations, which make them greatly invaluable for clinical applications. However, the molecular mechanism controlling differentiation of the Spg is still not clear. Among the discovered spermatogenesis-related genes, c-kit seems to be expressed first by the Spgs thus may play a central role in switching on the differentiation process. Expression of Kit and the activation of the Kit/Kitl pathway coincide with the start of differentiation of Spgs. Several genes have been discovered to be related to the Kit/Kitl pathway. in this review, we have summarized the recent discoveries of c-kit and the Kit/Kitl pathway-related genes in the spermatogenic cells during different stages of spermatogenesis.