Exosomes derived from uMSCs promote hair regrowth in alopecia areata through accelerating human hair follicular keratinocyte proliferation and migration.

Alopecia areata (AA) is a complex genetic disease that results in hair loss due to an autoimmune-mediated attack on the hair follicle. Mesenchymal stem cells (MSCs) have great potential to induce hair regeneration due to their strong secretion ability and multidirectional differentiation. Recent studies have revealed that the therapeutic potential of MSCs comes from their secretion ability, which can produce large amounts of bioactive substances and regulate the key physiological functions of subjects. The secretion products of MSCs, such as vesicles, exosomes, and conditioned media, have significant advantages in preparing of biological products derived from stem cells. Human umbilical cord mesenchymal stem cells (uMSCs) are the best choice for exosome production. uMSCs are obtained from the human umbilical cord. The umbilical cord is easy to obtain, and the efficiency of uMSCs isolation and culture higher than that of obtaining MSCs from bone marrow or adipose tissue. In this study, we investigated the effects of exosomes released from uMSCs in AA mice. In summary, due to easy isolation and cultivation, simple preparation, and convenient storage, it is possible to obtain uMSCs, or uMSCs exosomes for research and clinical treatment.

Treatment of maternal syphilis for preventing congenital syphilis: an observational study of adherence to treatment recommendation in Suzhou, China, 2019-2021.

BACKGROUND: China is one of the countries that set the goal to eliminate mother-to-child transmission (EMTCT) of syphilis by a target date. Active screening for syphilis among pregnant women, followed by effective treatment of maternal syphilis, is critical for achieving the goal. The China health authority issued national implementation protocols to guide EMTCT practice in health facilities. METHODS: Within a cohort of infants born to mothers infected with syphilis, we obtained the data of regimens used for treatment of maternal syphilis from the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis and Hepatitis B, and analysed the physician's treatment behaviour and its associated factors in a public hospital in Suzhou of China. RESULTS: A total of 450 pregnant women who were positive for treponemal or non-treponemal antibody, or had previous infection with syphilis were included into the study for analysis. Of them, 260 (57.8%) were positive for both treponemal and non-treponemal antibodies (syphilis seropositivity), and 353 (78.4%) were treated for syphilis according to the protocol in which 123 (34.8%) were treated with two courses. Non-adherence to treatment recommended by the protocol for maternal syphilis was significantly associated with antenatal visits in the third trimester (AOR 6.65, 95% CI 2.20-20.07, P =0.001), being positive only for a treponemal test (AOR 5.34, 95% CI 3.07-9.29, P <0.001) or having a syphilis infection before the pregnancy (AOR 2.05, 95% CI 1.14-3.69, P =0.017), whereas the uptake of treatment for two treatment courses was associated with attending antenatal care in 2020 or before (AOR 3.49, 95% CI 1.89-6.42, P <0.001), being positive for treponemal and non-treponemal tests (AOR 5.28, 95% CI 2.78-10.06, P <0.001) or having non-treponemal antibody titre of ≥1:8 (AOR 3.71, 95% CI 1.77-7.78, P =0.001). CONCLUSIONS: Implementation of the current recommendation to offer a universal treatment for syphilis among all pregnant women who are shown to be positive for a treponemal test alone is challenging in some clinical settings in China.

Lentivirus-mediated subcutaneous JAM-A modification promotes skin wound healing in a mouse model by strengthening the secretory function and proliferation of fibroblasts.

A better understanding of the molecular regulation of wound healing may provide novel therapeutic targets. A previous study revealed that junctional adhesion molecule A (JAM-A)-modified mesenchymal stem cells promoted wound healing. However, whether direct JAM-A modification in the skin wound edge area accelerates the wound repair process is not clear. We determined whether JAM-A modification at the skin wound edge accelerated the wound healing process. We established JAM-A modification mouse wound models and mouse primary fibroblast cell models. Wound pictures were taken to compare the wound size. H&E staining was performed to monitor the morphology of the wound and quality of the newborn skin. CCK-8 assays and immunofluorescence (IF) for Ki67 were used to measure the cell proliferation of mouse primary fibroblasts. Quantitative real-time PCR, immunohistochemistry, IF, and Western blot analysis were used to detect bFGF and EGF expression in vivo and in vitro. The JAM-A-overexpressing group exhibited a smaller residual wound size than the control group at Day 7. Thicker epidermal layers and more hair follicle-like structures were found in the JAM-A-overexpressing group at Day 21. Cell proliferation capacity was higher in JAM-A-modified mouse fibroblasts. Elevated levels of bFGF and EGF were found in the JAM-A-modified group in vivo and in vitro. JAM-A modification significantly promoted fibroblast proliferation and wound healing. Increased levels of bFGF and EGF growth factors may be part of the mechanism.

Distribution and clinical significance of circulating CD8+CD28- regulatory T cells in the peripheral blood of patients with pulmonary tuberculosis.

BACKGROUND: Regulatory T cells (Treg cells) in the peripheral blood of patients with pulmonary tuberculosis (PTB) may be closely related to the progression of PTB. In this study, the distribution characteristics and clinical importance of CD8+CD28- Treg cells in patients with tuberculosis were systematically analyzed, and the role and importance of CD8+CD28- Treg cells in influencing the immune response and progression of tuberculosis were discussed, which will provide immunological indices and reference values for the clinical diagnosis of tuberculosis. METHODS: Flow cytometry, sputum smears and computed tomography imaging were used to analyze the distribution characteristics of CD8+CD28- Treg cells in the peripheral blood of patients with PTB and the correlation between CD8+CD28-Treg cells and clinical and immune indices. RESULTS: The percentages of CD4+CD25high and CD8+CD28- Treg cells in the peripheral blood of patients with PTB were significantly higher than those in the healthy control (HC) group. Further analysis showed that the percentage of CD4+CD25highTreg cells in the Stage II group was significantly higher than that in the HC group. The percentages of CD4+CD25high and CD8+CD28- Treg cells increased significantly in patients in the Stage II group. The proportion of CD8+CD28- Treg cells was directly proportional to the degree of positivity in sputum smears, while CD4+CD25highTreg cells did not exhibit this trend. The correlations between the percentage of CD4+CD25high and CD8+CD28- Treg cells and the percentage of lymphocyte subsets were examined. The percentage of CD8+CD28- Treg cells was negatively correlated with the percentage of CD4+T cells and positively correlated with the CD8+T cell percentage in the HC and PTB groups. The percentage of CD4 + CD25highTreg cells was positively correlated with the percentage of CD4+T cells only in the PTB group. CONCLUSIONS: This study was the first to show that the proportion of CD8+CD28- Treg cells in the peripheral blood of patients with PTB was significantly increased, and the increase in CD8+CD28- Treg cells was related to the progression of PTB, which may affect the proportion of immune cell subsets by inhibiting the immune response, resulting in the progression of PTB.

Temporal and spatial characterization of negative regulatory T cells in HIV-infected/AIDS patients raises new diagnostic markers and therapeutic strategies.

BACKGROUND: Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required. METHODS: Hundred HIV-infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD-1+T cells, CD4+PD-1high T cells, CD8+PD-1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation. RESULTS: The percentages of CD4+ PD-1+ T cells and CD4+ CD25high Tregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate-stage and late-stage disease had higher percentages of CD4+ PD-1+ T cells; however, the percentage of CD4+ CD25high Tregs only increased in the patients with late-stage disease. In addition, CD4+ PD-1+ T cells but not CD4+ CD25high Tregs were negatively correlated with the absolute CD4+ T cell count. Spatially, no correlations between CD4+ PD-1+ T cells and CD4+ CD25high Tregs were observed, which suggests these Tregs function differently during immunosuppression. CONCLUSIONS: This study characterized negative regulatory T cells in HIV-infected/AIDS patients at both temporal and spatial scales and found that CD4+ CD25+ Tregs and CD4+ PD-1+ T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression.

H/ACA Box Small Nucleolar RNA 7A Promotes the Self-Renewal of Human Umbilical Cord Mesenchymal Stem Cells.

Human umbilical cord blood derived mesenchymal stem cells (uMSC) are pluripotent cells that have been now considered as a promising candidate for various cell-based therapies. However, their limited in vitro proliferation ability and the gradual loss of pluripotency set barricades for further usages. Emerging evidence suggests that small nucleolar RNAs (snoRNA) are actively involved in cell proliferation especially in tumor cells, but their roles in stem cells are largely unknown. In this study, we demonstrated that H/ACA box small nucleolar RNA 7A (SNORA7A) is inversely correlated to the decreased proliferation rate during in vitro passaging of uMSC. Further investigations indicate that SNORA7A overexpression can promote uMSC proliferation and self-renewal. The inhibition of SNORA7A using antisense oligonucleotides significantly reduces the expression and the binding of SNORA7A to DKC1, core protein that essential to form small nucleolar ribonucleo-particles (snoRNP) complex and catalyze pseudouridines in 28S RNA. And the inhibition also significantly suppresses uMSC proliferation and self-renewal. Moreover, overexpression of SNORA7A transcripts with mutations of binding regions for snoRNP core proteins and 28S RNA did not induce proliferation and self-renewal. Besides, SNORA7A also suppresses both the osteogenic and adipogenic differentiation, strengthening its self-renewal maintaining roles in uMSC. Taken together, our study for the first time showed that H/ACA box snoRNAs are actively involved in MSC proliferation as well as pluripotency control, and we identify SNORA7A as one of the critical snoRNAs that regulate the proliferation and self-renewal of uMSC through snoRNP recruiting. Stem Cells 2017;35:222-235.

More significance of TB-IGRA except for the diagnose of tuberculosis.

OBJECTIVE: Tuberculosis (TB)-interferon gamma release assay (IGRA) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between TB-IGRA test results and body's immune cells, disease progression and prognosis, which is explored in this study. DESIGN: A retrospective study was carried out on positive TB-IGRA patients who were infected with TB and diagnosed at our hospital from January 2014 to June 2015. The TB-IGRA, routine blood test, T-cell subgroup data were collected for statistical analysis. RESULTS: TB-IGRA results were in positive proportion to the lymphocytes, CD4+ T cells and CD4+ CD28+ T cells, whereas negative to the Treg cells. Patient with unilateral pulmonary lesion had higher TB-IGRA than those with bilateral pulmonary lesions. After the stimulation of TB-specific antigen, the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T Tcells were both increased and the CD4+ IFN-γ+ T had positive correlation with the value of TB-IGRA. CONCLUSIONS: IFN-γ was tested with TB-IGRA in patients with TB by the specific TB T cells and correlated with the lymphocytes, while the lymphocytes also closely related to the host's anti-TB immunity and disease outcome. Hence the result of TB-IGRA could reflect the specific anti-TB immunity ability of the host, disease progression and prognosis. This study further expands the application scope of TB-IGRA technology in the diagnosis of TB and lays a foundation for clinical practice to understand the immunity state of the patients with TB and the application of auxiliary clinical immunity regulators.

Effects of forest regeneration practices on the flux of soil CO2 after clear-cutting in subtropical China.

Reforestation after clear-cutting is used to facilitate rapid establishment of new stands. However, reforestation may cause additional soil disturbance by affecting soil temperature and moisture, thus potentially influencing soil respiration. Our aim was to compare the effects of different reforestation methods on soil CO2 flux after clear-cutting in a Chinese fir plantation in subtropical China: uncut (UC), clear-cut followed by coppicing regeneration without soil preparation (CC), clear-cut followed by coppicing regeneration and reforestation with soil preparation, tending in pits and replanting (CCRP), and clear-cut followed by coppicing regeneration and reforestation with overall soil preparation, tending and replanting (CCRO). Clear-cutting significantly increased the mean soil temperature and decreased the mean soil moisture. Compared to UC, CO2 fluxes were 19.19, 37.49 and 55.93 mg m-2 h-1 higher in CC, CCRP and CCRO, respectively (P < 0.05). Differences in CO2 fluxes were mainly attributed to changes in soil temperature, litter mass and the mixing of organic matter with mineral soil. The results suggest that, when compared to coppicing regeneration, reforestation practices result in additional CO2 released, and that regarding the CO2 emissions, soil preparation and tending in pits is a better choice than overall soil preparation and tending.

An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells.

The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies showed that HDAC2 knockdown significantly increased histone acetylation, facilitated TET1 binding and DNA demethylation at the promoters of iPS cell maturation-related genes during the transition of pre-iPS cells to a fully reprogrammed state. We also found that HDAC2 competed with TET1 in the binding of the RbAp46 protein at the promoters of maturation genes and knockdown of TET1 markedly prevented the activation of these genes. Collectively, our data not only demonstrated a novel intrinsic mechanism that the HDAC2-TET1 switch critically regulates iPS cell maturation, but also revealed an underlying mechanism of the interplay between histone acetylation and DNA demethylation in gene regulation.

Critical regulation of miR-200/ZEB2 pathway in Oct4/Sox2-induced mesenchymal-to-epithelial transition and induced pluripotent stem cell generation.

Fibroblasts can be reprogrammed to induced pluripotent stem cells (iPSCs) by application of transcription factors octamer-binding protein 4 (Oct4), SRY-box containing gene 2 (Sox2), Kruppel-like factor 4 (Klf4), and c-Myelocytomatosis oncogene (c-Myc) (OSKM), but the underlying mechanisms remain unclear. Here, we report that exogenous Oct4 and Sox2 can bind at the promoter regions of mir-141/200c and mir-200a/b/429 cluster, respectively, and induce the transcription activation of miR-200 family during the OSKM-induced reprogramming. Functional suppression of miR-200s with specific inhibitors significantly represses the OSKM-caused mesenchymal-to-epithelial transition (MET, an early event in reprogramming of fibroblasts to iPSCs) and iPSC generation, whereas overexpression of miR-200s promotes the MET and iPSC generation. Mechanistic studies showed that miR-200s significantly repress the expression of zinc finger E-box binding homeobox 2 (ZEB2) through directly targeting its 3' UTR and direct inhibition of ZEB2 can mimic the effects of miR-200s on iPSC generation and MET process. Moreover, the effects of miR-200s during iPSC generation can be blocked by ZEB2 overexpression. Collectively, our findings not only reveal that members of the miR-200 family are unique mediators of the reprogramming factors Oct4/Sox2, but also demonstrate that the miR-200/ZEB2 pathway as one critical mechanism of Oct4/Sox2 to induce somatic cell reprogramming at the early stage.

Human embryonic mesenchymal stem cells alleviate pathologic changes of MRL/Lpr mice by regulating Th7 cell differentiation.

Recent evidence indicates that mesenchymal stem cells (MSC) derived from early embryonic tissues have better therapeutic ability as compared with adult tissue-derived stem cells. In the present study, we transplanted human early embryonic MSC (hMSC) into MRL/Lpr mice via tail vein injection to observe the therapeutic efficacy of hMSC and their impact on T helper 17 (Th17) cell differentiation in MRL/Lpr mice. Animals in hMSC treatment group received hMSC (1 × 106/200 µL) via the tail vein at the age of 16 and 19 weeks. We found that hMSC treatment prolonged the survival of MRL/Lpr mice without inducing tumorigenesis, reduced urine protein, and alleviated the renal pathologic changes. In addition, it reduced the proportion of Th17 cells in the spleen of MRL/Lpr mice and the serum interleukin 17 (IL-17) concentration. Our in vitro experiment also demonstrated that hMSC could secrete Th17 differentiation-related cytokines of PGE2, IL-10 and TGF-ß, and IFN-γ stimulation up-regulated the secretion of these immune regulating factors. The results of the present study suggest that hMSC therapy could alleviate systemic and local renal lesions in MRL/Lpr mice, probably by secreting immune regulating factors and regulating Th17 cell differentiation in MRL/Lpr mice.

JAM-A promotes wound healing by enhancing both homing and secretory activities of mesenchymal stem cells.

The homing ability and secretory function of mesenchymal stem cells (MSCs) are key factors that influence cell involvement in wound repair. These factors are controlled by multilayer regulatory circuitry, including adhesion molecules, core transcription factors (TFs) and certain other regulators. However, the role of adhesion molecules in this regulatory circuitry and their underlying mechanism remain undefined. In the present paper, we demonstrate that an adhesion molecule, junction adhesion molecule A (JAM-A), may function as a key promoter molecule to regulate skin wound healing by MSCs. In in vivo experiments, we show that JAM-A up-regulation promoted both MSC homing to full-thickness skin wounds and wound healing-related cytokine secretion by MSCs. In vitro experiments also showed that JAM-A promoted MSC proliferation and migration by activating T-cell lymphoma invasion and metastasis 1 (Tiam1). We suggest that JAM-A up-regulation can increase the proliferation, cytokine secretion and wound-homing ability of MSCs, thus accelerating the repair rate of full-thickness skin defects. These results may provide insights into a novel and potentially effective approach to improve the efficacy of MSC treatment.

Ca(2+) and EGF induce the differentiation of human embryo mesenchymal stem cells into epithelial-like cells.

The mesenchymal to epithelial transition (MET) occurs in organ development and anti-tumorigenesis. We have investigated the effects of calcium (Ca(2+)) and epidermal growth factor (EGF) on human mesenchymal stem cell (hMSCs) differentiation into epithelial-like cells. hMSCs lost their biological characteristics after EGF transfection, and MET was achieved by adding 0.4 mmol Ca(2+). Western blotting and immunofluorescence showed expression of EGF, keratin, keratin 19 (K19), ß1-integrin, E-cadherin and phosphorylated focal adhesion kinase (p-FAK, Ser-910) increased in hMSCs infected with EGF and exposed to Ca(2+), although Smad3 activation was downregulated. hMSCs co-stimulated with EGF transfection and Ca(2+) can therefore differentiate into epithelial-like cells in vitro.

Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging.

Owing to its constant exposure to the external environment and various stimuli, skin ranks among the organs most vulnerable to manifestations of aging. Preventing and delaying skin aging has become one of the prominent research subjects in recent years. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential. MSC-derived extracellular vesicles (MSC-EVs) are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior. Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory, anti-oxidative stress, and wound healing promoting abilities. This review presents the latest progress of MSC-EVs in delaying skin aging. It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts, reducing the expression of matrix metalloproteinases, resisting oxidative stress, and regulating inflammation. We then briefly discuss the recently discovered treatment methods of MSC-EVs in the field of skin anti-aging. Moreover, the advantages and limitations of EV-based treatments are also presented.

Biomimetic Structure Hydrogel Loaded with Long-Term Storage Platelet-Rich Plasma in Diabetic Wound Repair.

Exploring the preparation of multifunctional hydrogels from a bionic perspective is an appealing strategy. Here, a multifunctional hydrogel dressing inspired by the characteristics of porous extracellular matrix produced during Acomys wound healing is prepared. These dressings are printed by digital light processing printing of hydrogels composed of gelatin methacrylate, hyaluronic acid methacrylate, and pretreated platelet-rich plasma (PRP) to shape out triply periodic minimal surface structures, which are freeze-dried for long-term storage. These dressings mimic the porous extracellular matrix of Acomys, while the freeze-drying technique effectively extends the storage duration of PRP viability. Through in vivo and in vitro experiments, the biomimetic dressings developed in this study modulate cell behavior and facilitate wound healing. Consequently, this research offers a novel approach for the advancement of regenerative wound dressings.

Bioinspired engineering ADSC nanovesicles thermosensitive hydrogel enhance autophagy of dermal papilla cells for androgenetic alopecia treatment.

Androgenic alopecia (AGA) is a highly prevalent form of non-scarring alopecia but lacks effective treatments. Stem cell exosomes have similar repair effects to stem cells, suffer from the drawbacks of high cost and low yield yet. Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes, enabling them to efficiently encapsulate substantial quantities of therapeutic proteins. In this study, we observed that JAM-A, an adhesion protein, resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages, thereby facilitating the process of hair regrowth in cases of AGA. Consequently, adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles (JAM-AOE@NV). The incorporation of JAM-AOE@NV into a thermosensitive hydrogel matrix (JAM-AOE@NV Gel) to effectively addresses the limitations associated with the short half-life of JAM-AOE@NV, and resulted in the achievement of a sustained-release profile for JAM-AOE@NV. The physicochemical characteristics of the JAM-AOE@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro. The JAM-AOE@NV Gel, thus, presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.

A 10-year mono-center study on patients with burns ≥70% TBSA: prediction model construction and multi-center validation: retrospective cohort.

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

MiR-138 promotes induced pluripotent stem cell generation through the regulation of the p53 signaling.

Induced pluripotent stem (iPS) cells, especially those reprogrammed from patient somatic cells, have a great potential usage in regenerative medicine. The expression of p53 has been proven as a key barrier limiting iPS cell generation, but how p53 is regulated during cell reprogramming remains unclear. In this study, we found that the ectopic expression of miR-138 significantly improved the efficiency of iPS cell generation via Oct4, Sox2, and Klf4, with or without c-Myc (named as OSKM or OSK, respectively), without sacrificing the pluripotent characteristics of the generated iPS cells. Exploration of the mechanism showed that miR-138 directly targeted the 3' untranslated region (UTR) of p53, significantly decreasing the expression of p53 and its downstream genes. Furthermore, the ectopic expression of p53 having a mutant 3'-UTR, which cannot be bound by miR-138, seriously impaired the effect of miR-138 on p53 signaling and OSKM-initiated somatic cell reprogramming. Combined with the fact that miR-138 is endogenously expressed in fibroblasts, iPS cells, and embryonic stem cells, our study demonstrated that regulation of the p53 signaling pathway and promotion of iPS cell generation represent an unrevealed important function of miR-138.

[Expression of PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients and its biological significance].

OBJECTIVE: To analyze the expression of co-stimulatory molecules PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients, and to explore its biological significance. METHODS: One hundred and thirty-three lung cancer patients, 25 lung infection patients and 23 healthy donors were enrolled in this study. 100 µl of whole blood from these subjects were collected. Multi-color immunofluorescence staining and flow cytometry were used to detect PD-1/PD-L1 expression. The results were statistically analyzed. RESULTS: The expression level of CD3⁺CD8⁺ T cells in the lung cancer patients was (38.83 ± 1.74)%, significantly lower than that in the control group [(43.25 ± 3.35)%, P < 0.05]. CD8⁺CD28⁺ T cell subset in the peripheral blood of lung cancer patients was (17.73 ± 1.21)% significantly lower than that of the healthy donors [(27.96 ± 2.72)%, P < 0.01]. The CD8⁺CD28⁻ T cell subset was (21.19 ± 1.92)% in the lung cancer patients, significantly higher than that of the healthy control group [(15.18 ± 2.93)%, P < 0.05]. The expression level of PD-1 on the surface of CD8⁺CD28⁺ T cells was (10.67 ± 1.12)% in the group of lung cancer patients, significantly higher than that of the control group [(5.32 ± 1.58)%, P < 0.01]. It was also found that the expression of PD-1 on CD8⁺CD28⁻ T cells was up-regulated in the group of lung cancer patients (7.46 ± 1.25)%, significantly higher than that of the healthy control group [(2.68+1.07)%, P < 0.01]. The expression level of PD-L1 on CD68⁺ cells in the lung cancer patients was (16.03 ± 2.06)%, significantly higher than that of the healthy control group [(9.32 ± 2.00)%, P < 0.05]. CONCLUSION: Up-regulation of PD-1/PD-L1 on peripheral blood cells in lung cancer patients negatively regulates the lymphocytes, inhibits the immune response for killing tumor cells, and promotes tumor development and immune escape.