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Intrauterine adhesion (IUA) is an endometrial fibrosis disease caused by repeated operations of the uterus and is a common cause of female infertility. In recent years, treatment using mesenchymal stem cells (MSCs) has been proposed by many researchers and is now widely used in clinics because of the low immunogenicity of MSCs. It is believed that allogeneic MSCs can be used to treat IUA because MSCs express only low levels of MHC class I molecules and no MHC class II or co-stimulatory molecules. However, many scholars still believe that the use of allogeneic MSCs to treat IUA may lead to immune rejection. Compared with allogeneic MSCs, autologous MSCs are safer, more ethical, and can better adapt to the body. Here, we review recently published articles on the immunomodulation of allogeneic and autologous MSCs in IUA therapy, with the aim of proving that the use of autologous MSCs can reduce the possibility of immune rejection in the treatment of IUAs.

Female infertility impacts the quality of life and well-being of affected individuals and couples. Female reproductive diseases, such as primary ovarian insufficiency, polycystic ovary syndrome, endometriosis, fallopian tube obstruction, and Asherman syndrome, can induce infertility. In recent years, translational medicine has developed rapidly, and clinical researchers are focusing on the treatment of female infertility using novel approaches. Owing to the advantages of convenient samples, abundant sources, and avoidable ethical issues, mesenchymal stem cells (MSCs) can be applied widely in the clinic. This paper reviews recent advances in using four types of MSCs, bone marrow stromal cells, adipose-derived stem cells, menstrual blood mesenchymal stem cells, and umbilical cord mesenchymal stem cells. Each of these have been used for the treatment of ovarian and uterine diseases, and provide new approaches for the treatment of female infertility.

Objective To observe the effects of prolonged exposure to high concentrations of PM2.5 on the trachea and lungs of mice and to determine whether the damages to the trachea and lung are induced by necroptosis. Methods Six- to eight-week-old female Balb/C mice of PM group were restrained in an animal restraining device using a nose-only “PM2.5 online enrichment system” for 8 weeks, in Shijiazhuang, Hebei, China. Anti -Fas group was exposed to PM2.5 inhalation and anti-Fas treatment via intranasal instillation. The mice in the control group inhaled filtered clean air. PM2.5 sample was collected and analyzed. Airway Hyperresponsiveness (AHR) was tested. Lung tissue and bronchoalveolar lavage fluid (BALF) were analyzed for Hematoxylin and eosin (HE) staining, electron microscopy, cellular inflammation, cytokines, Tunel, Fas, RIPK3 and MLKL expression. Results Compared to the other two groups, PM group displayed significantly increased AHR, neutrophils in BALF, significant bronchitis and alveolar epithelial hyperplasia and inflammation and necroptosis which were indicated by increased TUNEL, Fas, RIPK3 and MLKL measure. Conclusion Our findings suggest that PM2.5 can enhance AHR and these changes are induced by necroptosis-related inflammation.

Background The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGel™3D transplantation to activate the BMP7-Smad5 signaling pathway to treat intrauterine adhesions (IUA). Methods Autologous ADSCs were isolated and then merged with ShakeGel™3D. The IUA model was established by mechanical injury. The third generation of autologous ADSCs was injected directly into the uterus in combination with ShakeGel™3D. After 7 days of treatment, endometrial morphology, number of endometrial glands, endometrial fibrosis area, and fibrosis biomarker analysis by RT-PCR and IHC were examined. BMP7 and phosphorylation of Smad5 were also detected, and the recovery of infertility function in treated mice was evaluated. Results Fluorescence-activated cell sorting (FACS) showed that autologous ADSCs expressed CD105 (99.1%), CD29 (99.6%), and CD73 (98.9%). Autologous ADSCs could still maintain a good growth state in ShakeGel™3D. Histological examination revealed that the number of endometrial glands increased significantly, and the area of fibrosis decreased. At the same time, the expression of BMP7 and Smad5 in the ADSCs + Gel group was significantly upregulated, and the final reproductive function of this group was partly recovered. Conclusions Autologous ADSCs can be used in combination with ShakeGel™3D to maintain functionality and create a viable three-dimensional growth environment. The combined transplantation of autologous ADSCs and ShakeGel™3D promotes the recovery of damaged endometrial tissue by increasing BMP7-Smad5 signal transduction, resulting in endometrium thickening, increased number of glands, and decreased fibrosis, leading to restoration of partial fertility.

Diamide resistant phenotypes have evolved in the field and the resistance has been attributed to target-site mutations in some lepidopteran pests. In this study, we documented the resistance status of Chilo suppressalis to chlorantraniliprole during 2016-2018 in seven provinces of China. To investigate the possible role of target-site mutations as known from lepidopterans, we sequenced respective domains of the RyR gene of C. suppressalis with different levels of diamide resistance. The results revealed that I4758M (corresponding to I4790M in P. xylostella), Y4667D/C (numbered according to C. suppressalis), G4915E (corresponding to G4946E in P. xylostella), and one novel Y4891F (numbered according to C. suppressalis) RyR target-site mutations were present. The contribution of these mutations was further investigated by diamide toxicity bioassays with eight genome modified Drosophila melanogaster lines. The study showed that genome modified flies bearing the Y4667D mutation (corresponding to the Y4667D and I4758M simultaneous mutation in C. suppressalis) exhibited high resistance ratios to chlorantraniliprole (1542.8-fold), cyantraniliprole (487.9-fold) and tetrachlorantraniliprole (290.1-fold). The M4758I and G4915E simultaneous mutations (corresponding to single G4915E mutation in C. suppressalis) showed high resistance ratios to chlorantraniliprole (153.1-fold) and cyantraniliprole (323.5-fold), and relatively low resistance to flubendiamide (28.9-fold) and tetrachlorantraniliprole (25.2-fold). These findings suggest that multiple point mutations in RyR confer diamide resistance of C. suppressalis. The results contribute to a better understanding of insect diamide resistance mechanisms and provide insights on the impact of RyR target-site mutations in insects.

Background: Fine particulate matter (PM2.5) exacerbates airway inflammation and hyperreactivity in patients with asthma, but the mechanism remains unclear. The aim of this study was to observe the effects of prolonged exposure to high concentrations of PM2.5 on the pathology and airway hyperresponsiveness (AHR) of BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA) and to observe the effects of apoptosis and T-cell immunoglobulin and mucin domain 1 (TIM-1) in this process. Methods: Forty female BALB/c mice were divided into four groups: control group, OVA group, OVA/PM group, and PM group (n = 10 in each group). Mice in the control group were exposed to filtered clean air. Mice in the OVA group were sensitized and challenged with OVA. Mice in the OVA/PM group were sensitized and challenged as in the OVA group and then exposed to PM2.5 for 4 h per day and 5 days per week for a total of 8 weeks using a nose-only "PM2.5 online enrichment system" in The Second Hospital of Hebei Medical University. Mice in the PM group were exposed to the PM2.5 online enrichment system only. AHR was detected. Bronchoalveolar lavage fluid (BALF) was collected for cell classification. The levels of interleukin-4 (IL-4), IL-5, and IL-33 in BALF were measured using enzyme-linked immunosorbent assay. Changes in histological structures were examined by light microscopy, and changes in ultramicrostructures were detected by electron microscopy. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay in the lung tissues. Western blotting and immunohistochemistry were utilized to analyze the expression of Bcl-2, Bax, and TIM-1 in the lungs. Results: The results showed that AHR in the OVA/PM group was significantly more severe than that in the OVA and PM groups (P < 0.05). AHR in the PM group was also considerably more severe than that in the control group (P < 0.05). The BALF of OVA/PM group (28.00 ± 6.08 vs. 12.33 ± 4.51, t = 4.631, P = 0.002) and PM group (29.00 ± 3.00 vs. 12.33 ± 4.51, t = 4.927, P = 0.001) had more lymphocytes than the BALF of the control group. The number of neutrophils in the BALF of the OVA/PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) and PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) was much higher than those in the BALF of OVA group (P < 0.05). TUNEL assays showed that the number of apoptotic cells in the OVA/PM group was significantly higher than that in the OVA group (Tunel immunohistochemical scores [IHS%], 1.20 ± 0.18 vs. 0.51 ± 0.03, t = 8.094, P < 0.001) and PM group (Tunel IHS%, 1.20 ± 0.18 vs. 0.51 ± 0.09, t = 8.094, P < 0.001), and that the number of apoptotic cells in the PM group was significantly higher than that in the control group (Tunel IHS%, 0.51 ± 0.09 vs. 0.26 ± 0.03, t = 2.894, P = 0.020). The concentrations of IL-4 (77.44 ± 11.19 vs. 48.02 ± 10.02 pg/ml, t = 4.595, P = 0.002) and IL-5 (15.65 ± 1.19 vs. 12.35 ± 0.95 pg/ml, t = 3.806, P = 0.005) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.48 ± 0.10, t = 9.654, P < 0.001) and TIM-1/β-actin ratio (0.78 ± 0.11 vs. 0.40 ± 0.06, t = 6.818, P < 0.001) in the OVA/PM group were increased compared to those in the OVA group. The concentrations of IL-4 (77.44 ± 11.19 vs. 41.47 ± 3.40 pg/ml, t = 5.617, P = 0.001) and IL-5 (15.65 ± 1.19 vs. 10.99 ± 1.40 pg/ml, t = 5.374, P = 0.001) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.97 ± 0.16, t = 5.000, P = 0.001) and TIM-1/β-actin ratio (0.78 ± 0.11 vs. 0.31 ± 0.06, t = 8.545, P < 0.001) in the OVA/PM group were increased compared to those in the PM group. The concentration of IL-4 (41.47 ± 3.40 vs. 25.46 ± 2.98 pg/ml, t = 2.501, P = 0.037) and the Bax/Bcl-2 ratio (0.97 ± 0.16 vs. 0.18 ± 0.03, t = 7.439, P < 0.001) and TIM-1/β-actin ratio (0.31 ± 0.06 vs. 0.02 ± 0.01, t = 5.109, P = 0.001) in the PM group were also higher than those in the control group. Conclusions: Exacerbated AHR associated with allergic asthma caused by PM2.5 is related to increased apoptosis and TIM-1 activation. These data might provide insights into therapeutic targets for the treatment of acute exacerbations of asthma induced by PM2.5. Key words: Apoptosis; Asthma; Fine Particulate Matter; T-cell Immunoglobulin and Mucin Domain 1

Objective This study aimed to determine the impact of a ketogenic diet (KD) on neurobehavioral development when used to treat children with intractable epilepsy, confirming the efficacy of the KD, as well as the correlation between early electroencephalography (EEG) changes in the early stage with treatment efficacy. Methods We enrolled 42 children who were starting treatment for intractable epilepsy with the classic KD protocol. The total development quotient as well as the development quotients for adaptability, gross motor movements, fine motor movements, language, and individual–social interaction on the Gesell developmental scales were assessed before and after 3, 6, 12, and 18 months of KD treatment. The efficacy assessment was based on changes in seizure frequency after KD as recorded by the parents. We conducted 24-h video-EEG before and after 1 month of KD treatment. Results Developmental quotients of five energy regions in the Gesell developmental scales assessment were used to compare adaptability (P1 = 0.000), gross motor movements (P2 = 0.010), and fine motor movements (P3 = 0.000); the results showed significant differences. After KD treatment at different time points, 69.0%, 54.8%, 40.5%, and 33.3% patients, respectively, achieved a ≥ 50% reduction in seizure frequency. The reduction of epileptiform discharges in the awake state after 1 month of KD treatment correlated with the efficacy after 3 months of KD treatment. Conclusions Ketogenic diet treatment tends to be associated with improved neurobehavioral development, and more significant improvement can be obtained with prolonged treatment. The KD is safe and effective in treating children with intractable epilepsy. Early EEG changes correlate with clinical efficacy, to a certain degree.

BACKGROUND HIF-1α plays an important role in hypoxia-ischemia brain damage. Accumulating evidences demonstrates that HIF-1α can contribute to cell autophagy. Oxygen-glucose deprivation (OGD) is a commonly used ischemic model in vitro. Our study was performed to investigate the influences of HIF-1α on autophagy in SH-SY5Y cells under OGD treatment. MATERIAL AND METHODS An OGD model was constructed in SH-SY5Y cells. PI method and MTT assay were used to test cell death and viability, respectively. Western blot assay was used to estimate the protein levels of HIF-1α and LC3. Quantitative GFP-LC3 light microscopy autophagy assay was performed for SH-SY5Y cells. 2ME2 and siRNA-HIF-1α were applied to investigate the effects of HIF-1α-knockdown on LC3 expression. Additionally, 3-MA (autophagy inhibitor) and autophagy inducer rapamycin (Rapa) were used to investigate the effects of autophagy on cell survival under OGD condition. RESULTS Under OGD, the apoptosis of SH-SY5Ycells was increased while cell viability rate was decreased. The expression of HIF-1α was increased along with the advancement of OGD treatment and achieved the highest level at 24 h. However, inhibiting HIF-1α expression decreased the cell apoptosis and increased cell viability. LC3-II expression was gradually increased with the duration of OGD condition and knockdown of HIF-1α resulted in decreased expression of LC3. Inhibiting autophagy significantly enhanced the viability and reduced the apoptosis of SH-SY5Y cells, while enhancing autophagy showed the opposite effects. CONCLUSIONS Enhanced expression of HIF-1α may be related to autophagy activation in SH-SY5Y cells, thus contributing to ischemic/hypoxic brain damage.

Background Ambient fine particulate matter (PM2.5) could induce lung injury. Aryl hydrocarbon receptor (AhR) is involved in the molecular mechanisms of prooxidative and pro-inflammatory effect of PM2.5. Molecular hydrogen has antioxidant properties. The protective effect and mechanism of hydrogen on PM2.5-induced lung injury remain unclear. Objectives This study aimed to determine whether hydrogen could alleviate lung injury in a rat model of subacute exposure to concentrated ambient PM2.5, and explore the mechanism related to AhR. Methods Male Wastar rats were exposed to either concentrated ambient particles (CAPs) (diameter: ≤2.5 μm, average concentration: 1328 ± 730 μg/m3) or filtered air (FA) by nose-only inhalation (5 h/day, 5 days/week for 4 weeks). Hydrogen-treated rats inhaled 66.7% hydrogen from water electrolysis for 2 h after each exposure to CAPs or FA. Results CAPs inhalation induced lung injury, as demonstrated by pulmonary function decrease, histopathological damage, mucus hypersecretion [Periodic acid-Schiff (PAS) staining for mucins, immunohistochemistry and quantitative real-time PCR (RT-qPCR) for mucin 5AC (MUC5AC) expression], increased pro-inflammatory cytokines (TNF-α, IL-8 and IL-1β) and oxidative damage indexes [malondialdehyde (MDA) and 8-isoprostane F2α (8-iso-PG)]. While, hydrogen inhalation significantly alleviated the damages mentioned above. In addition, low expression of AhR in lung tissues determined by Western Blot was found after CAPs exposure, whereas hydrogen inhibited AhR decline induced by CAPs. Conclusions High concentrations of hydrogen could ameliorate pulmonary dysfunction, airway mucus hypersecretion, oxidation damage, and inflammation response in rats exposed to concentrated ambient PM2.5. Additionally, hydrogen alleviates lung injury induced by PM2.5 possibly through AhR-dependent mechanisms.

Ras homologue gene family member A (RhoA) is involved in tumor mobility, invasion, and metastasis. We detected RhoA expression in vulvar squamous cell carcinoma (VSCC) tissue, measured RhoA expression in the VSCC cell phenotype, and measured the expression of the relevant molecules after RhoA small interfering RNA (siRNA) transfection in SW962 cells. RhoA has a higher expression level in VSCC than normal vulva skin tissue and was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and differentiation; besides, VSCC patients with lymph node metastasis had higher positive RhoA expression. RhoA messenger RNA and protein expression was significantly reduced in the RhoA siRNA transfectants as compared with the negative control (NC) and mock-transfected cells (p