Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells.

Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. Furthermore, genome-wide occupancy and overexpression studies in Th17 cells revealed that Blimp-1 co-localized with transcription factors RORγt, STAT-3, and p300 at the Il23r, Il17a/f, and Csf2 cytokine loci to enhance their expression. Blimp-1 also directly bound to and repressed cytokine loci Il2 and Bcl6. Taken together, our results demonstrate that Blimp-1 is an essential transcription factor downstream of IL-23 that acts in concert with RORγt to activate the Th17 inflammatory program.

Orphan cytokine reveals IL-17 family secret.

The biology of interleukin-17C (IL-17C) has remained largely a mystery for more than a decade. Chang et al. (2011), in this issue of Immunity, and two other reports (Song et al., 2011; Ramirez-Carrozzi et al., 2011) demonstrate that IL-17C has broad functions in a variety of tissues.

Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2.

T helper 17 (Th17) cell development is driven by cytokines including transforming growth factor-ß (TGF-ß), interleukin-6 (IL-6), IL-1, and IL-23. Regulatory T (Treg) cells can provide the TGF-ß in vitro, but their role in vivo remains unclear, particularly because Treg cells inhibit inflammation in many models of Th17 cell-associated autoimmunity. We used mice expressing Diphtheria toxin receptor under control of the Foxp3 promoter to deplete Foxp3(+) Treg cells in adult mice during in vivo Th17 cell priming. Treg cell depletion resulted in a reduced frequency of antigen-specific IL-17 producers in draining lymph nodes and blood, correlating with reduced inflammatory skin responses. In contrast, Treg cells did not promote IL-17 secretion after initial activation stages. Treg cell production of TGF-ß was not required for Th17 cell promotion, and neither was suppression of Th1 cell-associated cytokines. Rather, regulation of IL-2 availability and resultant signaling through CD25 by Treg cells was found to play an important role.

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.

Sperm cryopreservation for Chinese male cancer patients: a 17-year retrospective analysis in an assisted reproductive unit in Hong Kong.

OBJECTIVE: To review sperm cryopreservation usage rates, corresponding reproductive outcomes, and the current situation in our locality. DESIGN: Retrospective case series. SETTING: Assisted Reproductive Technology Unit of the Department of Obstetrics and Gynaecology, Prince of Wales Hospital and the Chinese University of Hong Kong. PARTICIPANTS: There were 130 Chinese male patients who underwent sperm cryopreservation before proceeding to gonadotoxic treatment from January 1995 to January 2012. MAIN OUTCOME MEASURES: Demographic data, type of cancers and treatments, semen analysis, and reproductive outcomes. RESULTS: The median patient age was 27 (range, 15-43) years. Most (85%) were single at the time of referral. Over half of the patients (51%) had testicular cancer. Five patients declined sperm cryopreservation after counselling. Among the remaining 125 men, 122 men were able to produce sperm by masturbation but 12 were found to have azoospermia, leaving a total of 110 who proceeded to semen cryopreservation. There were no significant differences in semen parameters between different cancer types. After gonadotoxic treatment, in up to 32% (n=11/34) of the patients, semen analysis yielded deterioration; four patients had azoospermia. Four patients (4%, n=4/110) came back to use their thawed semen for in-vitro fertilisation (intracytoplasmic sperm injection), which resulted in three successful singleton pregnancies. CONCLUSION: Sperm cryopreservation is a simple and effective way of preserving the fertility potential of male patients undergoing gonadotoxic treatment. This procedure is underutilised and deserves increased awareness by all possible means.

Long-term reproductive outcome after hysteroscopic proximal tubal cannulation--an outcome analysis.

BACKGROUND: The optimal therapeutic method for proximal tubal obstruction (PTO) has yet to be defined. In addition, the reported successful recanalisation rate and reproductive outcome from hysteroscopic proximal tubal cannulation have been inconsistent. AIMS: To examine the morbidity and efficacy of laparoscopic-hysteroscopic proximal tubal cannulation for treating PTO. MATERIAL AND METHODS: This was a retrospective study evaluating 70 infertile women with PTO who underwent laparoscopic-hysteroscopic proximal tubal cannulation in The Prince of Wales Hospital, a university-affiliated hospital, from January 2005 to December 2010. Demographical data and operative details were reviewed. Women were then contacted by phone and completed a structured questionnaire. Recanalisation rate, intra-operative complication, pregnancy rates and pregnancy outcomes were examined. RESULTS: Fifty women had successful proximal cannulation on at least one side of the tube, providing an overall successful recanalisation rate of 71.4% per woman and 67.0% per tube. The overall pregnancy rate after successful hysteroscopic proximal cannulation of at least one tube is 55%. The overall mean time to become pregnant from natural conception or via clomiphene induction after successful unilateral or bilateral hysteroscopic cannulation was 10.5 ± 8.9 months. The procedure is associated with minimal morbidity. No prognostic factors were significantly associated with recanalisation and pregnancy rate. CONCLUSION: Laparoscopic-hysteroscopic cannulation for proximal obstruction is a procedure with minimal morbidity and a reasonable successful recanalisation rate. It should be considered as an alternative to in vitro fertilisation.

Pediatric emergency department-based rapid HIV testing: adolescent attitudes and preferences.

OBJECTIVE: The objective of this study was to describe adolescent attitudes/preferences toward rapid HIV testing in a pediatric emergency department (PED). METHODS: An anonymous survey was completed by adolescents who presented to an urban PED. The survey was completed while they participated in a rapid HIV prevention/testing program. Survey questions included demographics, HIV risk factors/knowledge, prior testing experience, and attitudes/preferences toward rapid HIV testing. RESULTS: One hundred fourteen adolescents between the ages of 14 and 21 years were surveyed. Most respondents (69%) reported that the emergency department was a very high preference location for testing. Eighty percent of adolescents agreed that they were more likely to get tested for HIV if a rapid test was available. Most participants strongly agreed that it was important to receive pretest and posttest counseling for HIV. In addition, 38% strongly agreed that they preferred a same-sex counselor, whereas 9% strongly agreed that they preferred a same-ethnicity counselor. Eighty-one percent reported that they planned to get retested for HIV in the next 6 to 12 months. CONCLUSIONS: This study offers valuable new insights into adolescent attitudes and preferences for rapid HIV testing in a PED. Adolescents gave high ratings to the location, testing, and counseling process. Our data support the importance of structured counseling, which is contrary to current published perspectives of counseling efficacy. In addition, we found that the PED was a highly preferred location for rapid HIV testing, which supports the need for increased development of prevention and testing programs in this setting.

Cost-Effectiveness of Evaluation of Children With Epilepsy in the Emergency Department: Need for Investment in Patient Education.

We aimed to study cost-effectiveness of seizure evaluation of children with epilepsy in the emergency department (ED). We reviewed epilepsy patients seen at our ED for 1 year. Age, laboratory and neuroimaging results, treatment, disposition, and usefulness of the visit (need for hospitalization, clinical improvement) were analyzed. We identified 330 patients, aged 23 days-21 years, 190 (57.5%) had blood tests, 45 (13.6%) urinalysis, 2 (0.6%) cerebrospinal fluid testing, and 44 neuroimaging studies (13.3%). Tests' positive yield were 41%, 11%, 0%, and 4.5%, respectively. One-third of patients (n = 122) were treated with antiepileptic drugs. Other treatments were administered to 44 (13.3%). One hundred eighteen patients (35.7%) were admitted to our hospital, 208 (63%) discharged to home. Two hundred eight visits were useful (63%). One-third of visits did not provide useful patient care. Their visits were expensive and not very cost-effective. Investment in patient education could decrease unnecessary ED visits.

Pediatric Hospital Discharges to Home Health and Postacute Facility Care: A National Study.

IMPORTANCE: Acute care hospitals are challenged to provide efficient, high-quality care to children who have medically complex conditions and may require weeks or months for recovery. Although the use of home health care (HHC) and facility-based postacute care (PAC) after discharge is well documented for adults, to our knowledge, little is known for children. OBJECTIVE: To assess the national prevalence of, characteristics of children discharged to, and variation in use across states of HHC and PAC for children. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 2,423,031 US acute care hospital discharges in 2012 for patients ages 0 to 21 years from the nationally representative Agency for Healthcare Research and Quality Kids' Inpatient Database. MAIN OUTCOMES AND MEASURES: Discharges to HHC (eg, visiting or private-duty home nursing) and PAC (eg, rehabilitation facility) were identified from Centers for Medicare and Medicaid Services Discharge Status Codes. We compared children's characteristics (eg, race/ethnicity and number of chronic conditions) by discharge type using generalized linear regression. RESULTS: The median age of participants was 3 years (interquartile range, 0-13 years), and 45.6% were female. Of 2,423,031 US acute care hospital discharges in 2012 for patients ages 0 to 21 years, 122,673 discharges (5.1%) were to HHC and 26,282 (1.1%) were to PAC facilities. Neonatal care was the most common reason (44.5%, n = 54,589) for acute care hospitalization with discharge to HHC. Nonneonatal respiratory, musculoskeletal, and trauma-related problems, collectively, were the most common reasons for discharge to PAC (42.9%, n = 11,275). When compared with PAC, more discharges to HHC had no chronic condition (34.4% vs 18.0%, P < .001) and fewer discharges to HHC had 4 or more chronic conditions (22.5% vs 37.7%, P < .001). In multivariable analysis, Hispanic children were less likely to use PAC (0.8% vs 1.1%; odds ratio [OR], 0.9 [95% CI, 0.8-0.9]) or HHC (3.3% vs 5.5%; OR, 0.8 [95% CI, 0.7-0.8]) compared with other children. Children with 4 or more chronic conditions compared with no chronic conditions had a higher likelihood of HHC use (11.0% vs 4.4%; OR, 2.9 [95% CI, 2.8-3.0]) and PAC (3.9% vs 0.8%; OR, 4.5 [95% CI, 4.3-4.9]). After case-mix adjustment, there was significant (P < .001) variation across states in HHC (range, 0.4%-24.5%) and PAC (range, 0.4%-4.9%) use. CONCLUSIONS AND RELEVANCE: Home health care and PAC use after discharge for hospitalized children is infrequent, even for children with multiple chronic conditions. It varies significantly by race/ethnicity and across states. Further investigation is needed to assess reasons for this variation and to determine for which children HHC and PAC are most effective.

Relief of vasomotor symptoms and vaginal atrophy with three doses of conjugated estrogens and medroxyprogesterone acetate in postmenopausal Asian women from 11 countries: The Pan-Asia menopause (PAM) study.

OBJECTIVE: To evaluate the efficacy of three doses of estrogen/progestin therapy for relief of vasomotor symptoms (VMS) and vaginal atrophy in Asian women of different ethnic background; to examine differences in prevalence of VMS among ethnic groups. METHODS: A prospective, randomized, double-blind multinational clinical trial in healthy postmenopausal women from 11 Asian countries. Following 2 weeks of baseline observations, the women received one of three conjugated estrogens (CE)/medroxyprogesterone acetate (MPA) doses (in mg) daily for 24 weeks: 0.625/2.5; 0.45/1.5; or 0.3/1.5. The women recorded VMS and uterine bleeding daily on diary cards translated into 10 languages. Vaginal responsiveness was evaluated by the vaginal maturation index (VMI) at baseline and at week 24. RESULTS: The study population consisted of 1028 postmenopausal women. The VMS-evaluable subpopulation was about 60% of the total population. The mean baseline hot flush frequency was 1.6 flushes/day (613 women). Hot flush frequency decreased significantly in all dose groups within 4 weeks of treatment. The VMI shifted significantly from immature (parabasal) to mature (superficial) cells at end of treatment. The therapeutic responses were comparable in all three groups. However, uterine bleeding was consistently less frequent in the 0.3/1.5 mg group. The percentage of women who reported VMS at baseline differed substantially among the different ethnic groups, ranging from 5% in Indonesian women to 100% in Vietnamese women. CONCLUSION: Asian postmenopausal women respond to CE/MPA therapy. The lowest dose is as effective for VMS and vaginal responsiveness as the higher doses, and the lowest dose is associated with the most favorable bleeding pattern. The prevalence of vasomotor symptoms differs among ethnic groups.

Prevalence of menopausal symptoms in different ethnic groups of Asian women and responsiveness to therapy with three doses of conjugated estrogens/medroxyprogesterone acetate: the Pan-Asia Menopause (PAM) study.

OBJECTIVE: To survey the prevalence of 18 menopausal symptoms in nine ethnic groups of Asian women. To evaluate responsiveness of symptoms to three estrogen/progestin doses in Asian women. DESIGN: A prospective, randomized, double-blind multinational clinical trial in 1028 healthy postmenopausal women from 11 Asian countries/regions. Following 2 weeks of baseline observations, the women received one of three conjugated estrogens (CE)/medroxyprogesterone acetate (MPA) doses (in mg) daily for 24 weeks: 0.625/2.5; 0.45/1.5; or 0.3/1.5. At baseline and throughout the study period, the women were asked to record each symptom daily on diary cards translated into 10 languages. RESULTS: The number of women in the different ethnic groups ranged from 24 (Malay) to 248 (Chinese). The overall prevalence of symptoms differed among the groups, with Vietnamese women generally reporting the highest rates. Within each ethnic group, the prevalence of individual symptoms varied substantially. Only 5% of Indonesian women, for example, reported hot flushes but 93% complained of body or joint aches/pains. Overall, body or joint aches/pains was the most prevalent symptom, ranging from 76% in Korean women to 96% in Vietnamese women. Therapy resulted in a significant decline in all symptoms. The decline was observed with all three doses after 4 weeks of treatment and continued throughout the 6-month study period. CONCLUSION: The prevalence of individual menopausal symptoms differed among ethnic groups of Asian women. Within each ethnic group the percentage of women reporting each symptom varied substantially. Symptoms declined after 4 weeks of hormone therapy and thereafter throughout the study. The effect of the lowest dose of CE/MPA (0.3/1.5 mg/day) was comparable to that of the higher doses.

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.

A randomized, placebo-controlled, crossover study of tibolone (Livial) on menopause symptoms, psychological well-being, and dyadic relationship of postmenopausal Chinese women and their spouses.

OBJECTIVE: To investigate the effects of 6-month treatment of tibolone on menopause symptoms, psychological well-being, and the dyadic relationship of postmenopausal Chinese women and their spouses. DESIGN: A randomized, double-blind, crossover study was conducted in 100 postmenopausal Hong Kong Chinese women who received tibolone (2.5mg/day) and placebo. At baseline, 6-month and 13-month visits, the women filled in the Greene Climacteric Scale (GCS), 12-item General Health Questionnaire (GHQ) and Dyadic Adjustment Scale (DAS), and their spouses completed GHQ and DAS. RESULTS: Both tibolone and placebo treatment were associated with a significant reduction in the GCS total scores after the first 6-month interventional period (95% CI: -8.0 to -2.5 for tibolone, and -5.7 to -0.7 for placebo). After the correction for placebo response, tibolone treatment was associated with a significant reduction in the GCS somatic subscore (-1.1 +/- 0.4 for tibolone group versus 0.6 +/- 0.5 for placebo group, P < 0.05). There were no significant changes in the GHQ and DAS total scores of the women and their spouses after tibolone treatment, both with and without the correction for placebo response. CONCLUSIONS: Tibolone treatment had a significant beneficial effect on the somatic menopause symptoms but had no effect on the psychological well-being or marital relationship of the postmenopausal Chinese women and their spouses.

Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause.

OBJECTIVE: Pueraria lobata (PL) is used as a traditional Chinese herbal remedy for menopausal symptoms, as well as an ingredient in preparations for conditions affecting menopausal women, such as osteoporosis, coronary heart disease, and some hormone-dependent cancers. The scientific basis for its action may be its action as a phytoestrogen. DESIGN: To examine the effects of PL in comparison with hormone replacement therapy (HRT) on lipid profile, sex hormone levels, bone turnover markers, and indices of cognitive function. For the study, 127 community-living, postmenopausal women aged 50 to 65 years were randomized to receive HRT (n = 43), PL (equivalent to 100 mg isoflavone; n = 45), or no treatment (n = 39) for 3 months. The following measurements were carried out at baseline and after 3 months for all participants: menopausal symptoms questionnaire; neuropsychological tests covering memory, attention, motor speed, and word-finding ability; quality of life (SF36); lipid profile; urinary deoxypyridinoline; dietary phytoestrogen intake and urinary phytoestrogen; estradiol; follicle-stimulating hormone; and luteinizing hormone. RESULTS: Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group. No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls. However, both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment. HRT and PL had different effects on cognitive function; HRT improved delayed recall, whereas flexible thinking seemed improved in the PL group. CONCLUSIONS: This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general. However, the effect of PL on cognitive function deserves further study.

A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being, and quality of life in postmenopausal Chinese women.

OBJECTIVES: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators. METHODS: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively. RESULTS: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo. CONCLUSIONS: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.

A prospective, randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women.

OBJECTIVES: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. METHODS: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. RESULTS: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (-0.02+/-0.03 g/cm(2)) while it increased by 2% in the 1 mg (0.02+/-0.03 g/cm(2)) and 3% in the 2 mg group (0.03+/-0.03 g/cm(2)). Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2) (-2%), 0.01+/-0.02 g/cm(2) (+1%) and 0.01+/-0.03 g/cm(2) (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip (P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip (P=0.82, 0.53, respectively). CONCLUSION: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.

Autoimmune memory T helper 17 cell function and expansion are dependent on interleukin-23.

Interleukin-23 (IL-23) is essential for the differentiation of pathogenic effector T helper 17 (Th17) cells, but its role in memory Th17 cell responses is unclear. Using the experimental autoimmune encephalomyelitis (EAE) model, we report that memory Th17 cells rapidly expanded in response to rechallenge and migrated to the CNS in high numbers, resulting in earlier onset and increased severity of clinical disease. Memory Th17 cells were generated from IL-17+ and RORγt+ precursors, and the stability of the Th17 cell phenotype depended on the amount of time allowed for the primary response. IL-23 was required for this enhanced recall response. IL-23 receptor blockade did not directly impact IL-17 production, but did impair the subsequent proliferation and generation of effectors coexpressing the Th1 cell-specific transcription factor T-bet. In addition, many genes required for cell-cycle progression were downregulated in Th17 cells that lacked IL-23 signaling, showing that a major mechanism for IL-23 in primary and memory Th17 cell responses operates via regulation of proliferation-associated pathways.

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.