RHC genotyping in Chinese Han population.

BACKGROUND: The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population. METHODS: In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D- were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and -292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test. RESULTS: The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%). CONCLUSIONS: None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.

The role of PKC in X-ray-induced megakaryocyte apoptosis and thrombocytopenia.

Thrombocytopenia is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte development and platelet production are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. Protein kinase C (PKC) plays an important role in regulating megakaryocyte development and platelet production. However, it remains unclear how PKC regulates IR-induced megakaryocyte apoptosis. In this study, we found that pretreatment of PKC pan-inhibitor Go6983 delayed IR-induced megakaryocyte apoptosis, and inhibited IR-induced mitochondrial membrane potential and ROS production in CMK cells. Moreover, suppressing PKC activation inhibited cleaved caspase3 expression and reduced p38 phosphorylation levels, and IR-induced PKC activation might be regulated by p53. In vivo experiments confirmed that Go6983 promoted platelet count recovery after 21 days of 3 Gy total body irradiation. Furthermore, Go6983 reduced megakaryocyte apoptosis, increased the number of megakaryocyte and polyploid formation in bone marrow, and improved the survival rate of 6 Gy total body irradiation. In conclusion, our results provided a potential therapeutic target for IR-induced thrombocytopenia.

Novel missense mutation c.797T>C (p.Met266Thr) gives rise to the rare B(A) phenotype in a Chinese family.

BACKGROUND AND OBJECTIVES: B(A) phenotype is usually formed by nucleotide mutations in the ABO*B.01 allele, with their products exhibiting glycosyltransferases (GTs) A and B overlapping functionality. We herein report a B(A) allele found in a Chinese family. MATERIALS AND METHODS: The entire ABO genes of the probands, including flanking regulatory regions, were sequenced through PacBio third-generation long-read single-molecule real-time sequencing. 3D molecular models of the wild-type and mutant GTB were generated using the DynaMut web server. The effect of the mutation on the enzyme function was predicted by PROVEAN and PolyPhen2. The predictions of stability changes were performed using DynaMut and SNPeffect. RESULTS: Based on serological and sequencing features, we concluded the two probands as possible cases of the B(A) phenotype. Crystallization analysis showed that Thr266 substitution does not disrupt the hydrogen bonds. However, some changes in interatomic contacts, such as loss of ionic interactions and hydrophobic contacts, and addition of weak hydrogen bonds, may have affected protein stability to some extent. This mutation was predicted to have a benign effect on enzyme function and slightly reduce protein stability. CONCLUSION: The probands had the same novel B(A) allele with a c.797T>C (p.Met266Thr) mutation on the ABO*B.01 backbone.

Microbial methanogenesis in aerobic water: A key driver of surface methane enrichment in a deep reservoir.

Significant amounts of the greenhouse gas methane (CH4) are released into the atmosphere worldwide via freshwater sources. The surface methane maximum (SMM), where methane is supersaturated in surface water, has been observed in aquatic systems and contributes significantly to emissions. However, little is known about the temporal and spatial variability of SMM or the mechanisms underlying its development in artificial reservoirs. Here, the community composition of methanogens as major methane producers in the water column and the mcrA gene was investigated, and the cause of surface methane supersaturation was analyzed. In accordance with the findings, elevated methane concentration of SMM in the transition zone, with an annually methane emission flux 2.47 times higher than the reservoir average on a large and deep reservoir. In the transition zone, methanogens with mcrA gene abundances ranging from 0.5 × 103-1.45 × 104 copies/L were found. Methanobacterium, Methanoseata and Methanosarcina were the three dominate methanogens, using both acetic acid and H2/CO2 pathways. In summary, this study contributes to our comprehension of CH4 fluxes and their role in the atmospheric methane budget. Moreover, it offers biological proof of methane generation, which could aid in understanding the role of microbial methanogenesis in aerobic water.

Enantioselective and Regiodivergent Synthesis of Propargyl- and Allenylsilanes through Catalytic Propargylic C-H Deprotonation.

We report a highly enantioselective intermolecular C-H bond silylation catalyzed by a phosphoramidite-ligated iridium catalyst. Under reagent-controlled protocols, propargylsilanes resulting from C(sp3)-H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less-hindered site was also observed. A variety of electrophilic silyl sources (R3SiOTf and R3SiNTf2), either commercial or in situ-generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3-enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η3-propargyl/allenyl Ir intermediate is generated upon π-complexation-assisted deprotonation and undergoes outer-sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step.

Polymorphisms in the promoter regions of RHD and RHCE genes in the Chinese Han population.

BACKGROUND AND OBJECTIVES: The Rh blood group system is the most polymorphic human blood group system. Previous studies have investigated variants in the RHD and RHCE promoter. The relevance of these variants to the Chinese Han population is further clarified in this study. MATERIALS AND METHODS: In total, 317 donors (223 Rh D-positive [D+], including 20 Del and 94 Rh D-negative [D-]) were randomly selected. The promoter regions and exon 1 of RHD and RHCE were amplified through polymerase chain reaction (PCR) whose products were directly sequenced using forward and reverse primers. RESULTS: Expected PCR products of the RHD promoter and exon 1 were amplified in 223 D+ individuals, including 20 Del individuals, and were absent in 81 of 94 D- individuals. Expected PCR products of RHCE were observed in all donors. Two single nucleotide variants (SNVs) were observed in the RHD promoter region. Moreover, 11 SNVs were observed in the promoter and exon 1 of RHCE. rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, rs2072931 and rs586178 with strong linkage disequilibria were significantly different between the D+ and D- groups. [A;C] was the most common haplotype in the RHD promoter (NC_000001.11:g.[-1033A>G;-831C>T]). [G;T;T;A;T;A;C;G;A;C;G] was the most predominant haplotype in both total and D- groups. In D+ individuals, [A;C;T;G;C;G;C;G;C;C;C] was the most frequent haplotype in the RHCE promoter (NC_000001.11:g.[-1080A>G;-958C>T;-390T>C;-378G>A;-369C>T;-296G>A;-144C>G;-132G>A;-122C>A;28C>T;48C>G]). CONCLUSION: We speculate that the SNVs/haplotypes found in this article cannot significantly affect gene expression. The present study findings should help elucidate the molecular basis of the polymorphic expression of RHD and RHCE promoter regions.

Sinomenine Hydrochloride Can Ameliorate Benign Prostatic Hyperplasia by Lowering the 5α-Reductase 2 Level and Regulating the Balance between the Proliferation and Apoptosis of Cells.

Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.

Contraceptive use and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation.

Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52-0.75; P < 0.0001), which was driven by significant inverse associations with oral contraceptives (OR = 0.66; 95% CI 0.54-0.79; P < 0.0001) and contraceptive implants (OR = 0.30; 95% CI 0.12-0.73; P = 0.008). We observed a similar effect with use of injections (OR = 0.37; 95% CI 0.10-1.38; P = 0.14), but this did not achieve significance. No significant associations were observed between patterns of intrauterine device use and risk of ovarian cancer. Conclusions These findings support a protective effect of oral contraceptives and implants on risk of ovarian cancer among women with BRCA mutations. The possible protective effect of injections requires further evaluation.

Beyond the cyclopropyl ring formation: fungal Aj_EasH catalyzes asymmetric hydroxylation of ergot alkaloids.

Ergot alkaloids (EAs) are among the most important bioactive natural products. FeII/α-ketoglutarate-dependent dioxygenase Aj_EasH from Aspergillus japonicus is responsible for the formation of the cyclopropyl ring of the ergot alkaloid (EA) cycloclavine (4). Herein we reconstituted the biosynthesis of 4 in vitro from prechanoclavine (1) for the first time. Additionally, an unexpected activity of asymmetric hydroxylation at the C-4 position of EA compound festuclavine (5) for Aj_EasH was revealed. Furthermore, Aj_EasH also catalyzes the hydroxylation of two more EAs 9,10-dihydrolysergol (6) and elymoclavine (7). Thus, our results proved that Aj_EasH is a promiscuous and bimodal dioxygenase that catalyzes both the formation of cyclopropyl ring in 4 and the asymmetric hydroxylation of EAs. Molecular docking (MD) revealed the substrate-binding mode as well as the catalytic mechanism of asymmetric hydroxylation, suggesting more EAs could potentially be recognized and hydroxylated by Aj_EasH. Overall, the newly discovered activity empowered Aj_EasH with great potential for producing more diverse and bioactive EA derivatives. KEY POINTS: • Aj_EasH was revealed to be a promiscuous and bimodal FeII/α-ketoglutarate-dependent dioxygenase. • Aj_EasH converted festuclavine, 9,10-dihydrolysergol, and elymoclavine to their hydroxylated derivatives. • The catalytic mechanism of Aj_EasH for hydroxylation was analyzed by molecular docking.

Actin polymerization regulates glycoprotein Ibα shedding.

Glycoprotein (GP) Ibα shedding mediated by ADAM17 (a disintegrin and metalloproteinase 17) plays an important role in negatively regulating platelet function and thrombus formation. However, the mechanism of GPIbα shedding remains elusive. Here, we show that jasplakinolide (an actin-polymerizing peptide)-induced actin polymerization results in GPIbα shedding and impairs platelet function. Thrombin and A23187-induced GPIbα shedding is increased by jasplakinolide; in contrast, GPIbα shedding is reduced by a depolymerization regent (cytochalasin B). We find that actin polymerization activates calpain leading to filamin A hydrolyzation. We further demonstrate that the interaction of filamin A with the cytoplasmic domain of GPIbα plays a critical role in regulating actin polymerization-induced GPIbα shedding. Taken together, these data demonstrate that actin polymerization regulates ADAM17-mediated GPIbα shedding, suggesting a novel strategy to negatively regulate platelet function.

Beyond the pill: contraception and the prevention of hereditary ovarian cancer.

BRCA1 and BRCA2 mutation carriers face an elevated lifetime risk of developing ovarian cancer. Oral contraceptives have been shown to significantly decrease the risk of ovarian cancer by approximately 50% in this high-risk population. Changes in contraceptive formulations and patterns of use over time have introduced lower hormonal dosages, different steroid types and non-oral routes of administration. Specifically, there has been a considerable shift in patterns of contraceptive use and the increase in the uptake of non-oral, long-acting, reversible contraception (e.g., intrauterine devices, implants, injections) has corresponded to a decline in oral contraceptive pill use. Whether or not these other methods confer a protective effect against ovarian cancer in the general population is not clear. To our knowledge, there have been no such studies conducted among BRCA mutation carriers. Furthermore, the impact of these changes on the risk of developing ovarian cancer is not known. In this article, we will review the existing epidemiologic evidence regarding the role of contraceptives and the risk of ovarian cancer with a focus on women with a BRCA1 or BRCA2 mutation. We will discuss recent findings and gaps in the knowledge while extrapolating from studies conducted among women from the noncarrier population.

Study of occlusal acoustic parameters in assessing masticatory performance.

BACKGROUND: Previous masticatory studies have focused on a variety of measurements of foods and boluses or kinematic parameters and sound during mastication. To date, the masticatory sound research of has been limited due to the difficulties of sound collection and accurate analysis. Therefore, significant progress in masticatory sound has not been made. Meanwhile, the correlation between acoustic parameters and mastication performance remains unclear. For the purpose of exploring the acoustic parameters in measuring mastication performance, the bone-conduction techniques and sound analysis were used, and a statistical analysis of acoustic and occlusal parameters were conducted. METHODS: The gnathosonic and chewing sounds of fifty-six volunteers with healthy dentate were recorded by a bone-conduction microphone and further analyzed by Praat 5.4.04 when intercuspally occluding natural foods (peanuts) were consumed. The granulometry of the expectorated boluses from the peanuts was characterized by the median particle size of the whole chewing sequence (D50a) and the median particle size during the fixed chewing strokes (D50b). The chewing time of the whole chewing sequence (CTa), the chewing time of the fixed chewing strokes (CTb), the chewing cycles (CC), and the chewing frequency (CF) were recorded and analyzed by the acoustic software. The acoustic parameters, including gnathosonic pitch, gnathosonic intensity, mastication sound pitch of the whole chewing sequence (MPa), mastication sound pitch of the fixed chewing strokes (MPb), mastication sound intensity of the whole chewing sequence (MIa) and mastication sound intensity of the fixed chewing strokes (MIb), were analyzed. Independent sample t-test, Spearman and Pearson correlation analyses were used where applicable. RESULTS: Significant difference in parameters CC, MIa, CF and D50a were found by sex (t-test, p < 0.01). The masticatory degree of the test foods was higher in women (CC, 24.25 ± 5.23; CF, 1.70 ± 0.21 s-1; D50a, 1655.07 ± 346.21 µm) than in men (CC, 18.14 ± 6.38; CF, 1.48 ± 0.18 s-1; D50a, 2159.21 ± 441.26 µm). In the whole chewing sequence study, a highly negative correlation was found between MIa and D50a, and a highly positive correlation was found between MIa and CF (r = - 0.94, r = 0.82, respectively, p < 0.01). No significant correlation was found between the remaining acoustic parameters and mastication parameters. In the fixed chewing strokes study, a highly negative correlation was found between MIb and D50b (r = - 0.85, p < 0.01). There was no significant correlation between the rest of the acoustic parameters and the mastication parameters. CONCLUSIONS: Mastication sound intensity may be a valuable indicator for assessing mastication. Acoustic analysis can provide a more convenient and quick method of assessing mastication performance.

Assessment of Skin Photoallergy Risk in Cosmetics Containing Herbal Extract Ingredients.

BACKGROUND/OBJECTIVE: In recent years, herbal extracts are becoming increasingly popular ingredients added in cosmetics; however, the assessment of their potential adverse effects on the skin remains unclear. As Coptis, Phellodendron amurense, curcumin, and shikonin are herbs currently used in cosmetic ingredients, the aim of this study was to assess their skin photoallergy (PA) potential and the concentrations at which they could safely be used. METHODS: In the patch test, Coptis, P. amurense, curcumin, and shikonin with 5, 10, 25, and 50% concentration were applied on 33 healthy Chinese subjects using the T.R.U.E. TEST® patch test system for 48 h. Photopatch testing was performed on 206 Chinese subjects with predisposed photosensitivity history using the Scandinavian photopatch series, and subjects were irradiated by 50% UVA minimum erythema dose. Photopatch testing of herbal extracts was then performed on subjects diagnosed with PA. RESULTS: Thirty-three subjects (14 with type III skin and 19 with type IV skin) completed contact patch testing of herbal extracts. Coptis induced a contact allergy (CA) reaction on 2 subjects at 25% concentration and on 2 subjects at 10% concentration. P. amurense induced a CA reaction on 1 subject at 10% concentration and on 1 subject at 5% concentration. Shikonin induced a stimulating reaction on 1 subject at 10% concentration. Curcumin induced a stimulating reaction on 1 subject at 10% concentration. Of the 206 Chinese subjects predisposed for photosensitivity, 10.19% had PA, 16.5% showed CA, and 1.45% had both PA + CA. PA-induced substances were promethazine hydrochloride (15%, n = 31), chlorpromazine hydrochloride (10.84%, n = 19), perfume mix (5.82%, n = 12), atranorin (3.39%, n = 7), 6-methyl coumarine (3.39%, n = 7), balsam Peru (1.94%, n = 4), fentichlor (1.94%, n = 4), 3,3',4',5-tetrachloro salicylanilide (0.97%, n = 2), hexachlorophene (0.97%, n = 2), chlorhexidine digluconate (0.97%, n = 2), and 4-aminobenzoic acid 2-hydroxy-4-methoxybenzophenone (0.97%, n = 2). Coptis at 25, 10, and 5% concentration and P. amurense, shikonin, and curcumin each at 10 and 5% concentration induced negative photopatch test results in all 10 photosensitive subjects. CONCLUSION: We have shown that Coptis, shikonin, or curcumin at 5% concentration in cosmetics could be applied safely without inducing contact allergic and photosensitive reactions on the skin. These findings advance the understanding of herbal extract use in cosmetic ingredients as related to the fields of dermatopharmacology and dermatotoxicology.

MEG3 interacted with miR-494 to repress bladder cancer progression through targeting PTEN.

The long noncoding RNA MEG3 is a significant tumor-suppressive gene in various tumors. But its biological role in bladder cancer remains uninvestigated. Herein, the biological mechanism of MEG3 in bladder cancer pathogenesis was explored. First, the expression of MEG3 in bladder cancer cells was examined, and we found that it was significantly reduced. In addition, in bladder cancer cells, we observed htat miR-494 was increased. Then, MEG3 was overexpressed in UMUC3 and SW780 cells and it could negatively modulate miR-494 expression. Bladder cancer cell proliferation was repressed, cell apoptosis was triggered and meanwhile, the cell cycle was remarkably arrested by the overexpression of MEG3. Moreover, the increase of MEG3 suppressed bladder cancer cell migration and invasion capacity. MEG3 can sponge miR-494 and the binding sites between them were confirmed by carrying out a series of functional assays. Furthermore, PTEN was speculated as a putative target of miR-494. Meanwhile, we found that miR-494 inhibitors induced PTEN. Finally, in vivo assays were conducted to prove that MEG3 can restrain bladder tumor growth by modulating miR-494 and PTEN. In conclusion, it was suggested MEG3 can interact with miR-494 to regulate PTEN in bladder cancer development.

Repair Effects of KGF on Ischemia-Reperfusion-Induced Flap Injury via Activating Nrf2 Signaling.

BACKGROUND: Ischemia-reperfusion (IR) injury is a main cause to and the mechanism of necrosis after flap transplantation. Researches were hardly conducted on the role and possible mechanism of keratinocyte growth factor (KGF) in association with IR flap injury. MATERIALS AND METHODS: A CoCl2-stimulated hypoxia cell model was established to investigate the effects of KGF on cell viability, apoptosis, cell cycle, and reactive oxygen species level. The experiments were performed by cell counting kit-8 and flow cytometry as required. Meanwhile, the expressions of cell cycle-related and nuclear factor E2-related factor 2 (Nrf2) signaling-related genes were determined using quantitative real-time PCR and Western blot. The right dorsolateral areas of Institute of Cancer Research mice were marked as flaps, the pedicle of which formed an IR process through clamping and loosening. Tissue morphologies were observed using hematoxylin and eosin staining 24 h after the surgery. The effects of KGF on cell apoptosis and associated genes expressions were studied by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, immunohistochemistry, and Western blot. RESULTS: HaCAT cells treated with 40 µM CoCl2 could not only reduce cell viability, promote cell apoptosis, arrest G1 phase of cell cycle and increase the activity of reactive oxygen species but also downregulate the expressions of c-myc, c-fos, transforming growth factor-α, Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase. Additional recombinant human KGF, on one hand, could protect the cells from hypoxia injury. On the other hand, recombinant human KGF could significantly inhibit cell apoptosis, increase KGF activity, and increase the Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase proteins levels in IR flap tissues. CONCLUSIONS: KGF played an important role in protecting mice flaps from IR injury, and the possible mechanism was involved in activating the Nrf2 signaling.

Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized, split-face, open-label, single-center study.

BACKGROUND: Topical drugs for mild to moderate acne include adapalene (ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic scheme. OBJECTIVES: To compare the safety and efficacy of 2% supramolecular SA (2% SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO +0.1%ADA) for treatment of facial acne. MATERIALS AND METHODS: This was an open-label, split face, randomized and single-centre clinical trial. Subjects with mild to moderate acne were enrolled. Two percent SSA cream were randomly applied on one side of the face while 5%BPO +0.1%ADA gel was applied on the opposite side for 28 days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14, and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time. RESULTS: A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO +0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all p > 0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L* value) and erythema (a* values) indicators showed no statistical differences in the left and right sides of the face (p > 0.05). CONCLUSION: This study demonstrated that 2% SSA has a similar efficacy with 5%BPO +0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.

Nucleoskeletal stiffness regulates stem cell migration and differentiation through lamin A/C.

Stem cell-based tissue engineering provides a prospective strategy to bone tissue repair. Bone tissue repair begins at the recruitment and directional movement of stem cells, and ultimately achieved on the directional differentiation of stem cells. The migration and differentiation of stem cells are regulated by nucleoskeletal stiffness. Mechanical properties of lamin A/C contribute to the nucleoskeletal stiffness and consequently to the regulation of cell migration and differentiation. Nuclear lamin A/C determines cell migration through the regulation of nucleoskeletal stiffness and rigidity and involve in nuclear-cytoskeletal coupling. Moreover, lamin A/C is the essential core module regulating stem cell differentiation. The cells with higher migration ability tend to have enhanced differentiation potential, while the optimum amount of lamin A/C in migration and differentiation of MSCs is in conflict. This contrary phenomenon may be the result of mechanical microenvironment modulation.

Certain BCG-reactive responses are associated with bladder cancer prognosis.

A subset of bladder patients does not respond to BCG treatment effectively and the underlying reason behind this observation is currently unclear. CD4+ T cells are composed of various subsets that each expresses a distinctive set of cytokines and can potently shift the immune response toward various directions. In this study, we examined the CD4+ T-cell cytokine response in bladder cancer patients toward BCG stimulation. We found that bladder cancer patients presented a variety of responses toward BCG, with no uniform characteristics. Those patients with high IFN-γ and IL-21 expression in CD4+ T cells presented significantly better prognosis than patients with low cytokine secretion in CD4+ T cells. Tumor-infiltrating CD4+ T cells were significantly less potent in expressing IFN-γ, IL-4, and IL-17, and more potent in expressing IL-10 than circulating CD4+ T cells. In addition, we found no difference in CD80, CD86, or MHC II expression by macrophages from patients with different IFN-γ and IL-21 levels. However, the secretion of IL-12, a Th1-skewing cytokine, was released at significantly higher level by macrophages from patients with high IFN-γ or high IL-21 secretion. We also identified that modulating monocytes/macrophages by GM-CSF-mediated polarization resulted in significantly elevated expression of IFN-γ and IL-21 from CD4+ T cells. Overall, these results suggested that the specific types of responses mounted by CD4+ T cells were critical to the final outcome of bladder cancer patients and can be influenced by monocyte/macrophage polarization.