Research progress on Th22 cells and related cytokines in tumors: current status and future perspectives.

Th22 cells are a newly identified subpopulation of CD4+ T lymphocytes distinct from Th1, Th2, and Th17 cells, which secretes mainly interleukin-22 (IL-22), in addition to a variety of other cytokines. The function of Th22 cells in tumors is mainly realized through IL-22, which can activate JAK/STAT and MAPK cell signaling pathways, thereby regulating the anti-tumor immune response of the body. The main function of Th22 cells is to participate in mucosal defense, tissue repair, and wound healing. However, controversial data have shown that overexpression of IL-22 can lead to pathological changes under inflammatory conditions and tumor progression. In this review, we searched the PubMed and Web of Science databases for articles and reviews published before May 6, 2022, using the keywords "Th22 cells, T helper 22 cells, cancer, tumor", and conducted a comprehensive review of the relevant literature. In addition, this article offers an overview of the relevant findings on the function of Th22 cells in tumors published in recent years, along with a more comprehensive analysis of the functions and mechanisms of Th22 cells in tumors. This article will hopefully inspire new future directions in the research on cancer therapy.

Clinical significance of regulatory T cells and T lymphocyte subsets in peripheral blood in neoadjuvant chemotherapy for breast cancer.

The impact of the immune response on the therapeutical efficacy of neoadjuvant chemotherapy for breast cancer remains largely unknown. To characterize the role of regulatory T cells (CD4+CD25+CD127lowTreg), T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+) and NK cells in neoadjuvant chemotherapy, we investigated the correlation patterns of these immune cell subsets with the progression of breast cancer. A total of 120 breast cancer patients receiving neoadjuvant chemotherapy in Nanjing Maternal and Child Health Hospital from May 2019 to November 2021 were retrospectively collected as the breast cancer group, and 46 healthy women were selected as the control group. The number of regulatory T cells, T lymphocyte subsets and NK cells in the peripheral blood were analyzed by flow cytometry. Compared with the control group, CD3+, CD4+, CD4+/CD8+ ratio and NK cells were significantly decreased in patients with breast cancer (P < 0.05), while the levels of Treg and CD8+ cells were significantly increased (P < 0.05). In addition, the status of the immune response among breast cancer patients at different clinical stages was obviously different. In higher tumor stages, the level of CD3+, CD4+, CD4+/CD8+ ratio and NK cell were reduced, while the level of Treg and CD8+ T cells gradually increased. Furthermore, we found a lower percentage of CD3+, CD4+, CD4+/CD8+ and NK cells in association with lymph node metastasis, accompanied by a higher number of CD8+ T cells. Interestingly, after treatment with neoadjuvant chemotherapy, the levels of Tregs, CD3+, CD4+ and CD4+/CD8+ ratio of patients were all upregulated compared with the levels before treatment, indicating the recovery of cytotoxic lymphocytes and a consolidation of the immunosuppressive microenvironment at the same time (P < 0.05). Immune dysfunction is commonly observed in breast cancer patients, which is closely associated with tumor progression and lymph node metastasis. Neoadjuvant chemotherapy was found to highly influence the number of T lymphocytes and improve the immune function of T lymphocyte subsets in breast cancer patients. At the same time, as immunosuppressive cells, the proportion of Tregs (CD4+CD25+CD127lowTreg) also increased after treatment with neoadjuvant chemotherapy. Our results provide guidance for the development of new combination strategies during neoadjuvant chemotherapy to reverse the immunosuppressive microenvironment and achieve better clinical outcomes.

Laboratory detection of SARS-CoV-2: A review of the current literature and future perspectives.

Nowadays, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose infectivity is awfully strong, has been a major global threat to the public health. Since lung is the major target of SARS-CoV-2, the infection can lead to respiratory distress syndrome (RDS), multiple organ failure (MOF), and even death. The studies on viral structure and infection mechanism have found that angiotensin-converting enzyme 2 (ACE2), a pivotal enzyme affecting the organ-targeting in the RAS system, is the receptor of the SARS-CoV-2 virus. Currently, the detection of SARSCoV-2 is mainly achieved using open plate real-time reverse-transcription polymerase chain reaction (RT-PCR). While open plate method has some limitations, such as a high false-negative rate, cumbersome manual operation, aerosol pollution and leakage risks. Therefore, a convenient method to rapidly detect SARS-CoV-2 virus is urgently and extremely required for timely epidemic control with the limited resources. In this review, the current real-time methods and principles for novel coronavirus detection are summarized, with the aim to provide a reference for real-time screening of coronavirus in areas with insufficient detection capacity and inadequate medical resources. The development and establishment of a rapid, simple, sensitive and specific system to detect SARS-CoV-2 is of vital importance for distinct diagnosis and effective treatment of the virus, especially in the flu season.

Research progress in breast cancer stem cells: characterization and future perspectives.

More and more studies have proved that there are a small number of cells with self-renewal and differentiation ability in breast tumors, namely breast cancer stem cells. Such cells play a key role in the initiation, development and migration of breast tumors. The properties of breast tumor stem cells are regulated by a range of intracellular and extracellular factors, including important signaling pathways, transcription factors, non-coding RNAs, and cytokines such as Hedgehog, Wnt, Notch, microRNA93, microRNA100, and IL-6. Tumor microenvironment (such as mesenchymal stem cells, macrophages and cytokines) plays an important role in the regulation of breast tumor stem cells. Using the keywords including "breast cancer stem cells", "signal pathway", "chemotherapy tolerance", and "non-coding RNA", "triple negative breast cancer", "inhibitors", this study retrieved the original articles and reviews published before October 3, 2021, from PubMed and WEB OF SCI database and this study performed a comprehensive review of them. After treatment, there is a correlation between the metastasis-prone nature and recurrence with breast cancer stem cells. The signaling pathway of breast cancer stem cells plays a significant role in activating the function of breast cancer cells, regulating the differentiation of breast cancer cells and controlling the division of breast cancer cells. This imbalance leads to the uncontrolled growth and development of breast cancer cells. Targeted therapy that blocks the corresponding pathway may become a new perspective for breast cancer treatment. In addition, corresponding therapeutic strategies can be used according to the expression characteristics of different molecular types of breast cancer stem cells. For ER-positive breast cancer, simultaneous endocrine therapy and targeted therapy of tumor stem cells may improve the efficacy of endocrine therapy. Trastuzumab therapy significantly reduces the risk of recurrence of HER2-positive breast cancer. For drug-resistant patients, combination therapy is required due to the different phenotypes of epithelial-mesenchymal transforming tumor stem cells. This study briefly reviews the research progress of breast cancer stem cell-related signaling pathways and their inhibitors, in order to provide a reference for breast cancer patients to obtain more effective clinical treatment.

Effect and mechanisms of reproductive tract infection on oxidative stress parameters, sperm DNA fragmentation, and semen quality in infertile males.

Recent years have seen a rising incidence of male infertility, mostly caused by the decline of sperm quality. The ratio of infertile males to infertile females has escalated from 3:7 in 2013 to current 5:5, which turns male infertility into the research focus of reproductive medicine. This study aimed to clarify the effect of reproductive tract infection by ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) on the DNA integrity and routine semen parameters of infertile males. A retrospective study was performed. A total of 259 infertile males who were treated at the Andrological Laboratory Examination and Reproductive Medicine Center in our hospital were analyzed. qRT-PCR was used to examine the infection status of CT and UU. According to the eligibility criteria, we evaluated the semen parameters and biochemical data of 253 men. Based on the results of PCR, the subjects were divided into four groups: Group I (CT positive, 63 cases), Group II (UU positive, 60 cases), Group III (CT positive and UU positive, 62 cases), and Group IV (no infection, 68 cases). DNA fragmentation index (DFI), sperm count, vitality and morphology, elastase level, seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed. Compared to Group IV, three groups (Group I, Group II and Group III) showed difference in semen volume, proportion of sperm with normal morphology, sperm motility, progressive motility, and vitality (P < 0.05). Compared to Group IV, Group II and Group III showed difference in DFI (P < 0.05). Compared to Group IV, Group II and Group III showed difference in elastase level (P < 0.05). VCL, VSL, VAP, WOB, ROS, TM, HDS showed differences between groups of abnormal/normal WBC (*P < 0.01).UU infection significantly increased the level of seminal leukocytes only in Group II, but not in the other three groups, indicating that UU is a factor to increase the level of seminal leukocytes. Compared with the normal leukocyte group, there were significant differences in total motility, forward motility and normal sperm ratio between the two groups. The proportion of sperm with abnormal morphology (mostly in the head) showed obvious difference between groups of high and normal seminal leukocytic levels. At the same time, in this study, SCGE and SCD verified that leukocytes could damage sperm DNA by increasing ROS, which ultimately affects male fertility.

Application of leukocyte subsets and sperm DNA fragment rate in infertile men with asymptomatic infection of genital tract.

BACKGROUND: About 15% of male infertility is due to genital tract infection and inflammation, some of them have no clinical symptoms, but manifested as leukocytospermia (LCS). Leukopenia will lead to functional impairment of male sperm and integrity damage of sperm morphology. A large amount of reactive oxygen species (ROS) produced by leukocytes can damage sperm nuclear DNA. The aim of this study was to investigate the correlation between leukocyte subsets and sperm DNA fragmentation rate in semen of infertile men with asymptomatic infection of genital tract. METHODS: One hundred and eight cases of infertile men were enrolled, who were admitted to our hospital from May 2016 to September 2018, and all had genital tract infections. After routine sperm analysis, realtime PCR was performed for detecting the infection of chlamydia trachoma (CT) and Ureaplasma urealyticum (UU). Furthermore, total leukocyte count in semen was evaluated by detection of CD45 molecules using immunocytochemistry. Flow cytometry was used for subset analysis, monocyte/macrophages were evaluated by CD14, and activated macrophages were evaluated by HLA-DR antigen. Sperm DNA fragmentation index (DFI) were evaluated by SCD method and 8-hydroxydeoxyguanosine (8-OHdG) expression were evaluated by chromatin diffusion method and TUNEL method; the correlation analysis was conducted between semen leukocyte subsets, sperm DNA fragment rate and conventional semen parameters. RESULTS: There was a significant correlation among the concentrations of cells expressing HLA-DR antigen and those expressing CD14 (P<0.01), but the concentrations of differential leukocyte subsets all had no significant correlation with sperm DFI, the percentage of 8-OHdG-expressing cells and routine semen parameters. The percentage of 8-OHdG-expressing sperm was positively correlated with the percentage of sperm fragments (r=0.42, P<0.01), and negatively correlated with sperm concentration (r=-0.32, P<0.01). After adjustment for possible confounders including age, abstinence time and smoking, the percentage of 8-OHdG-expressing sperms independently associated with sperm concentration (ß=-0.30; P=0.006) and DFI (ß=0.180, P=0.06). CONCLUSIONS: Among infertile men with genital tract infection, the sperm DFI is associated with decreased semen quality and not the concentration of differential leukocyte subsets.

Potential effects of COVID-19 on reproductive health: a mini review.

Coronavirus disease 2019 (COVID-19) is now a major public health problem worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is extremely strong. One major target of the virus is the lung, which can lead to death due to the development of respiratory distress syndrome and even multiple system organ failure. The possible pathophysiology by which SARS-CoV-2 affects the object is by way of the receptor, angiotensin-converting enzyme 2 (ACE2). From the study of the viral structure and infection mechanisms, researchers have discovered that the ACE2 acts as a receptor for SARS-CoV-2. According to previous studies, ACE2 is one of the key enzymes in the RAS system. Physiological functions can be found in angiosarcomas and in the kidney, liver, intestine and so on. Whether SARS-CoV-2 infection leads to male fertility impairment has recently received attention. Nevertheless, the association between SARS-CoV-2 infection and reproductive health is currently poorly understood. Using key words including "SARS-CoV-2", "reproductive health", "ACE2" and "2019-nCoV", we retrieved original articles and reviews from the PubMed and WEB OF SCI databases published before December 16, 2020 and performed a thorough review of them. Compared with females, we discovered that infected person with SARS-CoV-2 was higher in males. Men who were infected with SARS-CoV-2 may be easy to suffer from impaired reproductive health. These investigations would help for a comprehensive grasp of the relationship between SARS-CoV-2 infection and reproductive health.

Biological functions of circular RNAs and their roles in occurrence of reproduction and gynecological diseases.

Circular RNAs (circRNAs) are a large class of non coding endogenous RNAs in eukaryotic that are formed through 3'-5' ligation of a single RNA molecule. According to the different sources of the sequences, circRNA can be divided into three types: exon circRNA (ecRNA), intron circRNA (ciRNA), and exon-intron circRNA. Accumulating studies have shown that circRNAs are abundant, diverse, stable, and cell or tissue specific expression, etc. CircRNA plays a regulating role in gene expression, and an essential role in the process of biological development, such as miRNA sponges, endogenous RNAs and biomarkers, as well as critical role in the diagnosis of diseases. Studies have verified the interplay between circRNAs and the development of embryos, sperms, ovarian epithelial tumors, endometrial cancer and preeclampsia, suggesting the potential of circRNAs to become biomarkers or therapeutical targets for human diseases. In this paper, we reviewed the researches on circRNAs' characteristics, databases of circRNA, high-throughput sequencing of circRNA, and effect on reproductive and gynecological diseases.

Advances of Long Noncoding RNAs-mediated Regulation in Reproduction.

OBJECTIVE: Advances in genomics and molecular biology have led to the discovery of a large group of uncharacterized long noncoding RNAs (lncRNAs). Emerging evidence indicated that many lncRNAs function in multiple biological processes and its dysregulation often causes diseases. Recent studies suggested that almost all regulatory lncRNAs interact with biological macromolecules such as DNA, RNA, and protein. LncRNAs regulate gene expression mainly on three levels, including epigenetic modification, transcription, and posttranscription, through DNA methylation, histone modification, and chromatin remodeling. LncRNAs can also affect the development of diseases and therefore be used to diagnose and treat diseases. With new sequencing and microarray techniques, hundreds of lncRNAs involved in reproductive disorders have been identified, but their functions in these disorders are undefined. DATA SOURCES: This review was based on articles published in PubMed databases up to July 10, 2017, with the following keywords: "long noncoding RNAs", "LncRNA", "placentation", and "reproductive diseases". STUDY SELECTION: Original articles and reviews on the topics were selected. RESULTS: LncRNAs widely participate in various physiological and pathological processes as a new class of important regulatory factors. In spermatogenesis, spermatocytes divide and differentiate into mature spermatozoa. The whole process is elaborately regulated by the expression of phase-specific genes that involve many strains of lncRNAs. Literature showed that lncRNA in reproductive cumulus cells may contribute to the regulation of oocyte maturation, fertilization, and embryo development. CONCLUSIONS: LncRNA has been found to play a role in the development of reproduction. Meanwhile, we reviewed the studies on how lncRNAs participate in reproductive disorders, which provides a basis for the study of lncRNA in reproduction regulation.

Endoplasmic reticulum stress-induced apoptosis in the development of reproduction.

Proteins synthesized in the endoplasmic reticulum (ER) are properly folded with the assistance of ER chaperones. Accumulation of misfolded protein in the ER triggers an adaptive ER stress (ERS) response termed the unfolded protein response. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to reproductive response, including preimplantation embryos, testicular germ cell, placenta, and unexplained intrauterine growth restriction (IUGR). The major ERS pathway constituents are present at all stages of preimplantation development and that the activation of ERS pathways can be induced at the 8-cell, morula and blastocyst stage. This review mainly introduced the research progress of ERS induced apoptosis of reproductive cells, providing a new direction for the research of reproductive disease therapy.

Neurotoxicity and biomarkers of lead exposure: a review.

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Towards prenatal biomonitoring in Nanjing, China: lead and cadmium levels in the duration of pregnancy.

BACKGROUND: Prenatal lead and cadmium exposure will not only influence the mother' organ systems, but also will provide an environment that may influence the fetus and neonate in a harmful way.In the present study, we detected the blood lead levels (BLLS) and cadmium levels for the duration of pregnancy and 6-12 weeks after delivery and to analyze the influencing factors of BLLs in healthy pregnant women. METHODS: A cohort study survey was carried out. We recruited 174 healthy pregnant women without pregnancy or obstetric complications or abnormal pregnancy outcomes as the gravida group, and 120 healthy non-pregnant women as the control group. RESULTS: The lead concentrations in the three pregnancy trimesters and in the postpartum period were: (5.98 ± 2.43), (5.54 ± 2.01), (5.59 ± 1.97), and (6.76 ± 1.74) µg/dl; and (6.75 ± 2.13) µg/dl in the control group. The cadmium concentrations in the three pregnancy trimesters and postpartum period were 1.61 ± 0.45, 1.63 ± 0.46, 1.64 ± 0.49, and 1.67 ± 0.57. We found that the BLLs in the gravida group were lower than in the control group during all three trimesters. Occupations, supplement nutritional elements (dietary supplements and nutritional (food) elements), and the time of house painting could affect BLLs in pregnant women. Lead-related occupations, using cosmetics, and living in a house painted more recently than one year previously are risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors. CONCLUSIONS: These findings may help people, especially pregnant women, to reduce lead exposure via supplements of calcium, iron, zinc, and milk or avoiding contacting risk factors.

Blood lead levels during pregnancy and its influencing factors in Nanjing, China.

OBJECTIVE: To investigate the blood lead levels (BLLs) in the duration of pregnancy and 6-12 weeks after delivery, and analyze the influencing factors of BLLs in healthy pregnant women. METHODS: Pregnant women were recruited from September 2009 to February 2010 at the prenatal clinic in Nanjing Maternity and Child Health Care Hospital. Altogether 174 healthy pregnant women without pregnant or obstetric complications or abnormal pregnancy outcomes were enrolled as the gravida group, and 120 healthy non-pregnant women as the control group. BLLs during pregnancy were determined by flame atomic absorption spectroscopy. RESULTS: BLLs in all the three pregnancy trimesters and postpartum were 59.8±24.3, 55.4±20.1, 55.9±19.7, and 67.6±17.4 µg/L, respectively, and the mean BLL in control group was 67.5±21.3 µg/L. BLLs during all the three trimesters were lower in the gravida group than in the control group (P=0.043, 0.021, and 0.028). Furthermore, occupations, nutrients supplementation, and time of house/apartment painted were associated with BLLs in pregnant women. Lead-related occupations, cosmetics use, and living in a house painted less than 1 year before are risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors. CONCLUSION: Supplementing calcium, iron, zinc, and milk, or avoiding contact with risk factors may help people, especially pregnant women, to reduce lead exposure.

Breast milk lead and cadmium levels in suburban areas of Nanjing, China.

OBJECTIVE: To evaluate levels of lead (Pb) and cadmium (Cd) in the breast milk in the second postpartum month, to investigate the relationship between Pb/Cd levels in breast milk and some sociodemographic parameters, and to explore whether these levels affect the infants' physical status or the mothers' psychological status (postpartum depression). METHODS: A cross-sectional study was conducted between November 2009 and December 2010. Altogether 170 healthy mothers were enrolled from Nanjing Maternity and Child Health Care Hospital. The inclusion criteria were: voluntary to participate in this study, healthy, with no chronic disease, breastfeeding in the second postpartum month, living in a suburban but not non-industrial area of Nanjing, and not occupationally exposed to toxic metals. All the mothers completed a questionnaire and were evaluated based on the Edinburgh Postpartum Depression Scale (EPDS) to identify the risk of postpartum depression. Pb and Cd levels in breast milk were determined by inductively coupled plasma mass spectroscopy. The infants of these mothers were examined for their z scores of weight for age, length for age, head circumference for age, and body mass index for age. RESULTS: The median breast milk levels of Pb and Cd were 40.6 µg/L and 0.67 µg/L, respectively. In 164 (96.5%) of the 170 samples, Pb levels were higher than the limit reported by the World Health Organization (> 5 µg/L). Breast milk Cd level was > 1 µg/L in 54 (31.8%) mothers. The mothers with a history of anemia had a higher breast milk Pb level than those without a history of anemia (41.1 µg/L vs. 37.9 µg/L, P = 0.050). The median breast milk Cd level in those who were active and passive smokers during pregnancy was significantly higher than that in non-smokers (0.88 µg/L vs. 0.00 µg/L, P = 0.025). The breast milk Cd level in the mothers not taking iron and vitamin supplements for 2 months postpartum was higher than in those taking the supplements (iron supplement: 0.74 µg/L vs. 0.00 µg/L, P = 0.025; vitamin supplement: 0.78 µg/L vs. 0.00 µg/L, P = 0.005). Breast milk Cd level at the second postpartum month was negatively correlated with the z scores of head circumference (r = - 0.248, P = 0.042) and weight for age at birth (r =- 0.241, P = 0.024) in girls. No correlation was found between the breast milk Pb/Cd levels and the EPDS scores. CONCLUSION: Considering the high levels of Pb and Cd in breast milk in this study, breast milk monitoring programs are necessary.