USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway.

The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.

Bufalin targeting CAMKK2 inhibits the occurrence and development of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) accounts for about 15% of primary liver cancer, and the incidence rate has been rising in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to find its signature genes and therapeutic drug. Here, we studied that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the occurrence and metastasis of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. METHODS: IC50 of bufalin in ICC cells was determined by CCK8 and invasive and migratory abilities were verified by wound healing, cell cloning, transwell and Western blot. IF and IHC verified the expression of CAMKK2 between ICC patients and normal subjects. BLI and pull-down demonstrated the binding ability of bufalin and CAMKK2. Bioinformatics predicted whether CAMKK2 was related to the Wnt/ß-catenin pathway. SKL2001, an activator of ß-catenin, verified whether bufalin acted through this pathway. In vitro and in vivo experiments verified whether overexpression of CAMKK2 affects the proliferative and migratory effects of ICC. Transmission electron microscopy verified mitochondrial integrity. Associated Ca2+ levels verified the biological effects of ANXA2 on ICC. RESULTS: It was found that bufalin inhibited the proliferation and migration of ICC, and CAMKK2 was highly expressed in ICC, and its high expression was positively correlated with poor prognosis.CAMKK2 is a direct target of bufalin, and is associated with the Wnt/ß-catenin signaling pathway, which was dose-dependently decreased after bufalin treatment. In vitro and in vivo experiments verified that CAMKK2 overexpression promoted ICC proliferation and migration, and bufalin reversed this effect. CAMKK2 was associated with Ca2+, and changes in Ca2+ content induced changes in the protein content of ANXA2, which was dose-dependently decreasing in cytoplasmic ANXA2 and dose-dependently increasing in mitochondrial ANXA2 after bufalin treatment. In CAMKK2 overexpressing cells, ANXA2 was knocked down, and we found that reversal of CAMKK2 overexpression-induced enhancement of ICC proliferation and migration after siANXA2. CONCLUSIONS: Our results suggest that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the proliferation and migration of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. Thus, bufalin, as a drug, may also be used for cancer therapy in ICC in the future.

USP32 deubiquitinase: cellular functions, regulatory mechanisms, and potential as a cancer therapy target.

An essential protein regulatory system in cells is the ubiquitin-proteasome pathway. The substrate is modified by the ubiquitin ligase system (E1-E2-E3) in this pathway, which is a dynamic protein bidirectional modification regulation system. Deubiquitinating enzymes (DUBs) are tasked with specifically hydrolyzing ubiquitin molecules from ubiquitin-linked proteins or precursor proteins and inversely regulating protein degradation, which in turn affects protein function. The ubiquitin-specific peptidase 32 (USP32) protein level is associated with cell cycle progression, proliferation, migration, invasion, and other cellular biological processes. It is an important member of the ubiquitin-specific protease family. It is thought that USP32, a unique enzyme that controls the ubiquitin process, is closely linked to the onset and progression of many cancers, including small cell lung cancer, gastric cancer, breast cancer, epithelial ovarian cancer, glioblastoma, gastrointestinal stromal tumor, acute myeloid leukemia, and pancreatic adenocarcinoma. In this review, we focus on the multiple mechanisms of USP32 in various tumor types and show that USP32 controls the stability of many distinct proteins. Therefore, USP32 is a key and promising therapeutic target for tumor therapy, which could provide important new insights and avenues for antitumor drug development. The therapeutic importance of USP32 in cancer treatment remains to be further proven. In conclusion, there are many options for the future direction of USP32 research.

Chitosan oligosaccharide attenuates acute kidney injury and renal interstitial fibrosis induced by ischemia-reperfusion.

Acute kidney injury (AKI) and renal interstitial fibrosis are global clinical syndromes associated with high morbidity and mortality. Renal ischemia-reperfusion (I/R) injury, which commonly occurs during surgery, is one of the major causes of AKI. Nevertheless, an efficient therapeutic approach for AKI and the development of renal interstitial fibrosis is still lacking due to its elusive pathogenetic mechanism. Here, we showed that chitosan oligosaccharide (COS), a natural oligomer polysaccharide degraded from chitosan, significantly attenuates I/R-induced AKI and maintains glomerular filtration function by inhibiting oxidative stress, mitochondrial damage, and excessive endoplasmic reticulum stress both in vitro and in vivo. In addition, long-term administration of COS can also attenuate the proliferation of myofibroblasts, mitigate extra cellular matrix deposition, and thus inhibit the transition of AKI to chronic kidney disease through participating in metabolic and redox biological processes. Our findings provide novel insights into the protective role of COS against acute kidney injury.

Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway.

Gastric cancer (GC) is the most common malignant tumor of digestive system. Bufalin extracted from Venenum Bufonis is one of the most effective anticancer monomers, which has been proved to play anticancer roles in a variety of cancers such as ovarian cancer, prostate cancer and neuroblastoma. However, there are few studies on bufalin in GC, and lack of clear targets. The effect of bufalin on the proliferation and migration of GC cells was detected by CCK-8, scratch wound healing assay, transwell assay and Western blotting. The potential direct interaction proteins of bufalin were screened by human proteome microarray containing 21,838 human proteins. The target protein was determined by bioinformatics, and the binding sites were predicted by molecular docking technique. Biological experiments in vitro and in vivo were conducted to verify the effect of bufalin directly interaction protein and the mechanism of bufalin targeting the protein to inhibit the development of GC. The results showed that bufalin inhibited the proliferation and migration of MKN-45 and HGC-27 GC cell lines in vitro. BFAR, a direct interaction protein of bufalin has several potential binding sites to bufalin. BFAR is highly expressed in GC and promotes the occurrence and metastasis of GC by activating PI3K/AKT/mTOR signal pathway in vitro and in vivo. Bufalin reversed the promoting effect of BFAR on the carcinogenesis and metastasis of GC by down-regulating the expression of BFAR. Our results show that bufalin targeting BFAR inhibits the occurrence and metastasis of GC through PI3K/AKT/mTOR signal pathway. These results provide a new basis for bufalin as a promising drug for the treatment of GC.

C-Phycocyanin Ameliorates the Senescence of Mesenchymal Stem Cells through ZDHHC5-Mediated Autophagy via PI3K/AKT/mTOR Pathway.

The senescence of mesenchymal stem cells (MSCs) impairs their regenerative capacity to maintain tissue homeostasis. Numerous studies are focusing on the interventions and mechanisms to attenuate the senescence of MSCs. C-phycocyanin (C-PC) is reported to have multiple functions such as antitumor, antioxidation, anti-inflammation and anti-aging roles, but there is little research about the effects of C-PC on the senescence of MSCs. Here we investigated the roles and mechanism of C-PC on MSCs senescence. In vitro results showed that C-PC could reduce senescence, enhance proliferation, promote the adipogenic and osteogenic differentiation in senescent MSCs induced by oxidative stress. In vivo D-Galactose (D-Gal) induced rats aging models showed C-PC also increased the viability and differentiation of intrinsic senescent bone marrow derived MSCs (BMSCs). Furthermore, C-PC also decreased the levels of oxidative stress markers ROS or MDA, elevated the SOD activity, and increased the anti-inflammatory factors. Proteomic chip analysis showed that C-PC interacted with ZDHHC5, and their interaction was verified by pull down assay. Overexpression of ZDHHC5 aggravated the senescence of MSCs and greatly lessened the beneficial effects of C-PC on senescence. In addition, we found ZDHHC5 regulated autophagy by altering LC3, Beclin1 and PI3K/AKT/mTOR pathway. In summary, our data indicated that C-PC ameliorates the senescence of MSCs through zinc finger Asp-His-His-Cys (DHHC) domain-containing protein 5 (ZDHHC5) mediated autophagy via PI3K/AKT/mTOR pathway. The present study uncovered the key role of autophagy in MSCs senescence and PI3K/AKT/mTOR pathway may be a potential target for anti-senescence studies of MSCs.

Annexin A protein family: Focusing on the occurrence, progression and treatment of cancer.

The annexin A (ANXA) protein family is a well-known tissue-specific multigene family that encodes Ca2+ phospholipid-binding proteins. A considerable amount of literature is available on the abnormal expression of ANXA proteins in various malignant diseases, including cancer, atherosclerosis and diabetes. As critical regulatory molecules in cancer, ANXA proteins play an essential role in cancer progression, proliferation, invasion and metastasis. Recent studies about their structure, biological properties and functions in different types of cancers are briefly summarised in this review. We further discuss the use of ANXA as new class of targets in the clinical diagnosis and treatment of cancer.

Research progress in protein microarrays: Focussing on cancer research.

Although several effective treatment modalities have been developed for cancers, the morbidity and mortality associated with cancer continues to increase every year. As one of the most exciting emerging technologies, protein microarrays represent a powerful tool in the field of cancer research because of their advantages such as high throughput, small sample usage, more flexibility, high sensitivity and direct readout of results. In this review, we focus on the research progress in four types of protein microarrays (proteome microarray, antibody microarray, lectin microarray and reversed protein array) with emphasis on their application in cancer research. Finally, we discuss the current challenges faced by protein microarrays and directions for future developments. We firmly believe that this novel systems biology research tool holds immense potential in cancer research and will become an irreplaceable tool in this field.

Protective effect of C-phycocyanin and apo-phycocyanin subunit on programmed necrosis of GC-1 spg cells induced by H2 O2.

C-phycocyanin (C-PC) is an effective antioxidant and has an important value in medical research. Oxidative stress is considered to be one of the main underlying mechanisms of cell death, and reducing oxidative stress is one of the strategies to enhance germ cell viability. Herein, we investigated the protective effect and the mechanism of C-PC and apo-phycocyanin subunit on oxidative stress damage induced by H2 O2 in GC-1 spg cells. C-PC genes were cloned into the pGEX-4T-1 vectorand transformed into Escherichia coli BL21 to achieve the efficient expression of C-PC subunit. GC-1 spg cells were treated with 600 µM H2 O2 for 24 h to establish the oxidative stress damage model. Cell viability was detected by CCK-8. The degree of oxidative stress was detected by testing Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and glutathione (GSH) and Malondialdehyde (MDA) levels. Reactive oxygen species (ROS) was evaluated utilizingby 2', 7'-dichlorofluorescent-diacetate (DCFH-DA). Mitochondrial membrane potential was determined by JC-1. Cell necrosis rate was detected by Annexin V-FITC/PI. Expression of protein was detected by western blot. We found that C-PC and GST-CPC ß significantly inhibited H2 O2 -induced oxidative damage of GC-1 spg cells, improved the ability of antioxidation, reduced ROS overproduction, and mitochondrial membrane potential loss, and inhibited the RIP-1/RIP-3/ p-MLKL signaling pathway to reduce the necrosis rate. The results demonstrated that C-PC played a protective role against H2 O2 -induced cell damage, especially its ß subunit. This study provides a theoretical basis for C-PC as a potential protective agent of reproductive system.

The protective effect of C-phycocyanin in male mouse reproductive system.

C-phycocyanin from Spirulina platensis has pharmacological effects such as anti-oxidation, anti-cancer, anti-inflammatory and anti-atherosclerosis activities as well as liver and kidney protection. However, there is little research on C-phycocyanin applied in the field of reproductive medicine, and it is therefore the focus of the current study. In this study, a GC-1 spg cell model and male mouse reproductive injury model were constructed by TNF α + Smac mimetic + zVAD-fmk (TSZ) and cyclophosphamide (Cy), respectively. It has been proved that C-phycocyanin can increase cell viability and reduce cell death in GC-1 spg cells induced by TSZ. C-phycocyanin could protect the reproductive system of male mice from cyclophosphamide, improve spermatogenesis, sperm quality and fertility, increase the release of testosterone, stabilize the feedback regulation mechanism, and ensure the spermatogenic ability of mice. It could also improve the ability of anti-oxidation. In addition, C-phycocyanin could play a protective role by down-regulating RIPK1, RIPK3, and p-MLKL to inhibit the necroptotic signaling pathway. These results suggest that C-phycocyanin could protect GC-1 spg cells and the reproductive system of male mice from TSZ and cyclophosphamide, and the protective mechanism may be achieved by inhibiting the signal pathway of necroptosis. Therefore, C-phycocyanin could serve as a promising reproductive system protective agent. C-phycocyanin may enter public life as a health product in the future.

Preoperative Rim Enhancement on Magnetic Resonance Imaging Indicates Larger Tumor Size and Poor Prognosis in Chinese Basal-Like Breast Cancer Patients.

Background: This study was to investigate the prevalence of preoperative rim enhancement, and its association with clinicopathological features, relapse, and survival profiles in Chinese basal-like breast cancer (BC) patients. Materials and Methods: The preoperative breast magnetic resonance imaging images of 145 basal-like BC patients who underwent surgical excision were obtained to determine rim enhancement. Besides, based on disease status and survival status during follow-up, the 1-year relapse rate/mortality, 3-year relapse rate/mortality, 5-year relapse rate/mortality were calculated; disease-free survival (DFS) and overall survival (OS) were determined. Results: There were 51 (35.2%) patients with rim enhancement and 94 (64.8%) patients without rim enhancement. Furthermore, rim enhancement was associated with larger tumor size and advanced T stage, whereas it did not associate with age, pathological differentiation, N stage, or TNM stage. In addition, rim enhancement was associated with higher 1-, 3-, and 5-year relapse rate and shorter DFS; meanwhile, rim enhancement was associated with increased 1-, 3-, and 5-year mortality rate and decreased OS. By multivariate Cox's regression analyses, rim enhancement, pathological differentiation, and N stage independently predicted reduced DFS; T stage independently predicted declined OS. Conclusion: Preoperative rim enhancement on MRI might be a possible noninvasive indicator for guiding personalized treatment strategies and improving prognosis in Chinese basal-like BC patients.

A Review on Drug Delivery System for Tumor Therapy.

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.

[Effect of combination of acupuncture and psychological intervention on attention, response inhibition and cerebral blood flow in children with attention deficit hyperactivity disorder].

OBJECTIVE: To observe the clinical curative effect on attention deficit hyperactivity disorder (ADHD) and explore the relevant mechanism of acupuncture in treatment. METHODS: A total of 100 ADHD children were randomized into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases, 1 case dropped off). In the control group, the routine psychological intervention was used. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6), Baihui (GV 20), Sishencong (EX-HN 1), etc., once daily, for 3 months. The Cambridge neuropsychological tests automated battery (CANTAB) was adopted to evaluate attention and response inhibition in two groups before and after treatment. Digi-Lite color transcranial Doppler was used to measure cerebral arterial blood velocity. The therapeutic effect was compared between the two groups. RESULTS: Regarding evaluation of attention, the mean delay time in the observation group after treatment was shorter than that before treatment and that in the control group separately (P<0.05), and rapid visual information processing A' statistics (RVP A') value was higher than that before treatment and that in the control group separately (P<0.05). For evaluation of response inhibition, the number of Go signal error, the time of stop signal response and the number of stop Go signal error after treatment were all reduced as compared with those before treatment in the two groups (P<0.05). The number of stop signal error was also reduced after treatment as compared with that before treatment in the observation group (P<0.05). The number of Go signal error and the number of stop signal error in the observation were lower than those in the control group (P<0.05). After treatment, the average flow velocity of bilateral posterior cerebral artery (PCA) was increased than that before treatment in the two groups (P<0.05). The average flow velocity of the left middle cerebral artery (MCA-L) and bilateral anterior cerebral artery (ACA) after treatment was increased than that before treatment in the observation group (P<0.05), and the average flow velocity of left PCA, MCA-L and bilateral ACA in the observation group was faster than that in the control group (P<0.05). The total effective rate was 90.5% (19/21) in the observation group, remarkably higher than 50.0% (11/22) in the control group in children with attention deficit (P<0.05). The total effective rate was 83.3% (40/48) in the observation group, also higher than 63.3% (31/49) in the control group (P<0.05). CONCLUSION: Acupuncture combined with psychological intervention may improve attention and response inhibition in ADHD children, which is possibly related to the regulation of cerebral blood flow.

[Effect of maternal immune level at different pregnancy stages on cow's milk protein allergy in infants].

OBJECTIVE: To study the association between maternal Th1/Th2 immune level at different pregnancy stages and cow's milk protein allergy (CMPA) in infants. METHODS: The healthy women with a singleton pregnancy, as well as their offspring, who attended Yidu Central Hospital of Weifang and Qingzhou Traditional Chinese Medicine Hospital from July 2016 to December 2018 were enrolled. The maternal levels of interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) at the second and third trimesters of pregnancy were measured. A CMPA questionnaire survey was conducted within one year after birth. Food avoidance and cow's milk oral challenge tests were performed in infants suspected of CMPA. The 48 infants who met the diagnostic criteria for CMPA were included in the observation group, and the remaining 977 normal infants were included in the control group. A univariate analysis was performed on the infants with CMPA. A Poisson regression analysis was used to determine the association between maternal Th1/Th2 immune factors at different pregnancy stages and CMPA. RESULTS: The detection rate of CMPA was 4.68%. The clinical manifestations included the symptoms of the digestive system, skin, and respiratory system and other symptoms. The univariate analysis showed that compared with the control group, the observation group had significantly higher incidence rates of maternal food allergy and maternal history of allergic diseases (P<0.05) and a significantly lower breastfeeding rate (P<0.05). The observation group had significantly lower maternal levels of IL-2 (second and third trimesters) and IFN-γ (third trimester) than the control group (P<0.05). Maternal low IFN-γ at the third trimester and maternal low IL-2 at the second and third trimesters were significantly associated with CMPA in infants (P<0.05). After correction of the factors of breastfeeding, maternal food allergy, and maternal history of allergic diseases, it was found that maternal low IL-2 and IFN-γ at the third trimester were still significantly associated with CMPA in infants (P<0.05). CONCLUSIONS: The maternal decrease in Th1 level at the third trimester of pregnancy may lead to the change in fetal immunity and thus increase the risk of CMPA in offspring.

C-phycocyanin inhibits epithelial-to-mesenchymal transition in Caski cells.

BACKGROUND: In cervical cancer, most patients die of metastasis. The epithelial-to-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of cervical cancer. C-phycocyanin (C-PC) is a natural marine product isolated and purified from Spirulina platensis, has been investigated that has anti-cancer function. The aim of this study was to explore the inhibitory effect of C-phycocyanin on the migration and invasion of cervical cancer cells induced by transforming growth factor-ß1 (TGF-ß1), so as to provide a new idea for the treatment and prognosis of cervical cancer. METHODS: A wound-healing assay, an invasion assay, immunofluorescence assay, western blot, flow cytometry and real-time reverse transcriptione polymerase chain reaction were explored in cervical cancer Caski cell lines. TGF-ß/smad signaling pathway was evaluated of in Caski cell lines. RESULTS: Our study indicated that TGF-ß1 induced EMT in cervical cancer cells. C-phycocyanin inhibited EMT in Caski cells by down-regulating N-cadherin and up-regulating E-cadherin protein expression. Furthermore, C-phycocyanin could inhibit the expression and proteins Twist, Snail and Zeb1 transcription factors related to EMT. In addition, C-phycocyanin could inhibit the migration and invasion of Caski cells induced by TGF-ß1. Besides, C-phycocyanin inhibited EMT through TGF-ß/smads signaling pathway. We also found C-phycocyanin induced cell cycle G0/G1 arrest by decreasing protein expression levels of Cyclin D1 and p27. CONCLUSIONS: C-phycocyanin reversed TGF-ß1-induced epithelial-to-mesenchymal transition in cervical cancer cells and down-regulated the TGF-ß/samd signaling pathway induced G0/G1 arrest of tumor cell cycle.

Targeted Antitumor Mechanism of C-PC/CMC-CD55sp Nanospheres in HeLa Cervical Cancer Cells.

In vitro studies had shown that C-Phycocyanin (C-PC) inhibited cervical cancer HeLa cells growth. We constructed C-PC/CMC-CD55sp nanospheres using C-PC, Carboxymethyl Chitosan (CMC), and CD55 ligand peptide (CD55sp) to allow for targeted antitumor effects against HeLa cells in vitro and in vivo. The characteristics of the nanospheres were determined using FTIR, electron microscopy, and laser particle size analysis. Flow cytometry, laser confocal microscopy and small animal imaging system showed the targeting of C-PC/CMC-CD55sp nanospheres on HeLa cells. Subsequently, the proliferation and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), flow cytometry, TUNEL assay and electron microscopy. The expression of the apoptosis-related protein was determined using western blot. The stainings of Hematoxylin and Eosin (HE) were employed to evaluate the cell condition of tumor tissue sections. The cytokines in the blood in tumor-bearing nude mice was determined using ELISA. These results showed that C-PC/CMC-CD55sp nanospheres were successfully constructed and targeted HeLa cells. The constructed nanospheres were more effective than C-PC alone in inhibiting the proliferation and inducing apoptosis in HeLa cells. We also found that C-PC/CMC-CD55sp nanospheres had a significant inhibitory effect on the expression of antiapoptotic protein Bcl-2 and a promotion on the transformation of caspase 3 to cleaved caspase 3. C-PC/CMC-CD55sp nanospheres played an important role in tumor suppression, reduced the expression TGF-ß, and increased IL-6 and TNF-α. This study demonstrates that the constructed new C-PC/CMC-CD55sp nanospheres exerted targeted antitumor effects in vivo and in vitro which provided a novel idea for application of C-PC, and provided experimental basis for comprehensive targeted treatment of tumors.

Saturated fatty acids activate the inflammatory signalling pathway in Schwann cells: Implication in sciatic nerve injury.

Sciatic nerve injury affects quality of life. Many immune cells and inflammatory cytokines have been reported to be involved in sciatic nerve injury, but little is known about the ligands and receptors that trigger inflammatory responses. By using a modified sciatic nerve clamp injury method, we found that the recruitment of Schwann cells and the inflammatory response were enhanced after sciatic nerve injury. Toll-like receptor 4 (TLR4), one of the major members of the TLR family, is highly expressed in Schwann cells. Under certain conditions, myeloid differentiation protein 2 (MD2) binds to TLR4 on the membrane and plays important roles in the inflammatory response. The reductions in the recruitment of Schwann cells and the inflammatory response induced by the blockade of TLR4 or MD2 suggest that TLR4 and MD2 are involved in sciatic nerve injury. What are the endogenous signals that activate the inflammatory response? A large number of free saturated fatty acids (SFAs) are released from Schwann cells, adipocytes and the blood after sciatic nerve injury. Liang et al reported that Schwann cells can be stimulated by palmitic acid (PA). Here, we found that the expression and secretion of TNF-α and IL-6 were enhanced by PA treatment. Moreover, PA activated TLR4 signalling pathway-related proteins and stimulated a strong association between TLR4 and MD2. Blocking TLR4 or MD2 reversed the PA-induced inflammatory response and TLR4 downstream signalling pathway. Thus, we speculated that SFAs act as endogenous ligands that activate TLR4/MD2, thus triggering Schwann cell inflammation during sciatic nerve injury.

[Acupuncture combined with medication improves endocrine hormone levels and ovarian reserve function in poor ovarian response patients undergoing in vitro fertilization-embryo transplantation].

OBJECTIVE: To observe the clinical effect of acupuncture plus medication in the treatment of poor ovarian response (POR) patients and to explore its mechanisms in assisting pregnancy. METHODS: A total of 100 volunteer POR women undergoing in vitro fertilization-embryo transplantation (IVF-ET) were recruited in the present study. On the 1st cycle of IVF-ET, these POR women received microstimulation of ovulation program (oral administration of Clomiphene, muscular injection of Menotrophin, Chorionic Gonadotrophin triggering, etc.). Before receiving the 2nd period of IVF-ET, these patients were equally and randomly divided into control, medication (Climen, composed of estradiol valerate and cyproterone acetate), acupuncture and acupuncture+medication (combined treatment) groups according to the random number table. Patients of the medication group were asked to orally take Climen (1 tablet/d for 21 days) beginning from the 3rd day of the menstruation, which was repeated for 3 menstrual cycles. Patients of the acupuncture group received manual acupuncture stimulation of Guanyuan (CV4), and bilateral Taixi (KI3), Sanyinjiao (SP6) of and Tai-chong (LR3) from day 8 to 15 of menstruation (follicular phase), once daily for 3 menstrual cycles. On the 2nd day of menstruation of the 1st and 2nd IVF-ET cycle, the ovarian reserve function was detected, including measurement of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) contents by using radioimmunoassay, and serum anti-mullerian hormone (AMH) level by using ELISA, and the antral follicles count (AFC) of the ovaries by using a color Doppler ultrasonic diagnosis apparatus. At the end of ovulation induction, the assisted pregnancy indexes and outcomes were detected, including administration of dosage and days of gonadotropin (Gn), the diameter of dominant oocyte, level of E2 on the trigger day, the numbers of ultrasound-guided-retrieved oocyte and the cultivated high-quality embryo (grade 1 and 2). RESULTS: After the treatment, the contents of serum FSH, LH and E2 in the medication, acupuncture and combined treatment groups were significantly reduced (P<0.05), and the content of serum AMH and ovary AFC in the medication, acupuncture and combined treatment groups were obviously increased (P<0.05) in comparison with their own pre-treatment (P<0.05). Compared with the control group, the levels of FSH, LH and E2 contents were notably decreased, and the AMH content and AFC significantly increased in the medication, acupuncture and combined treatment groups (P<0.05). Comparison among the three treatment groups showed that the levels of FSH, LH and E2 were notably lower in the combined treatment group than in the acupuncture group (P<0.05), and the AFC was markedly more in the combined treatment group than in the acupuncture group (P<0.05), and LH content was also significantly lower in the combined treatment group than in the medication group (P<0.05). Regarding the pregnancy-assistant indexes and outcomes, the dosage of Gn in the combined treatment group and the number of Gn administration days in the acupuncture and combined treatment groups were significantly fewer (P<0.05), serum E2 levels on the trigger day in the medication, acupuncture and combined treatment groups, and the high-quality embryo number in the combined treatment group were considerably higher in comparison with their own levels of the 1st IVF-ET cycle in each group (P<0.05). Comparison among the three groups showed that the dosage and number of administration days of Gn in the combined treatment group were fewer than those in the medication group(P<0.05), and the dosage of Gn in the combined treatment group were significantly lower than that in the acupuncture group (P<0.05), E2 content of the combined treatment group was markedly higher than that of the medication and acupuncture groups (P<0.05). The high-quality embryo number in the combined treatment group was obviously larger than that of the medication group (P<0.05). No significant differences were found between the 2nd and 1st IVF-ET cycles in the number of the obtained oocyte, between the acupuncture and medication groups in the E2 content at the trigger day, and the numbers of Gn administration days and the high-quality embryo (P>0.05). CONCLUSION: Acupuncture combined with medication improves the level of endocrinal hormones and ovarian reservation function in POR women undergoing IVF-ET, benefiting the ovary environment of pregnancy.

STROBE-A preliminary investigation of IVIM-DWI in cardiac imaging.

This study aims to explore the possibility to apply intravoxel incoherent motion-magnetic resonance imaging (IVIM-MRI) in cardiac imaging.Multi-b-value diffusion-weighted imaging (DWI) sequence scanning was performed on 12 healthy volunteers. A double exponential model was adopted, and the b-value sequence was 0, 20, 60, 80, 120, 200, and 600 second/mm. The D-value, D*-value, and f-value of the anterior posterior and lateral walls of the ventricular septum were respectively measured on the short axis section of the heart, the parameters of the myocardium in different blood supply areas in each segment were recorded, and the measured data of these different segments were compared using analysis of variance.Among these 12 healthy volunteers, the D-value, D*-value, and f-value of these 72 segments were not exactly equal, the D-values of the myocardium in the 5th and 11th segment were lower than those in the 2nd, 3rd, 8th, and 9th segments, and the pairwise differences were statistically significant (P < .001). Furthermore, the difference in D-value between the 5th and 11th segments was not statistically significant (P = 1.000). The D*-value and f-value of the myocardium in the 5th and 11th segment were higher than those in the 2nd, 3rd, 8th, and 9th segments, and the pairwise differences were statistically significant (P < .001). Furthermore, the differences in D*-value and f-value between the 5th and 11th segments was not statistically significant (P = .214, .787).The intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) technique can quantitatively reflect the diffusion and blood perfusion status of the myocardium.

Controlling the ferroelectric and resistive switching properties of a BiFeO3 thin film prepared using sub-5 nm dimension nanoparticles.

In recent years, BiFeO3 has attracted significant attention as an interesting multiferroic material in the exploration of fundamental science and development of novel applications. Our previous study (Phys. Chem. Chem. Phys.18, 2016, 25409) highlighted the interesting physicochemical features of BiFeO3 of sub-5 nm dimension. The study also accentuated the existence of weak ferroelectricity at sub-5 nm dimensions in BiFeO3. Based on this feature, we have prepared thin films using sub-5 nm BiFeO3 nanoparticles and explored various physicochemical properties of the thin film. We report that during the formation of the thin film, the nanoparticles aggregated; particularly, annihilation of their nanotwinning nature was observed. Qualitatively, the Gibbs free energy change ΔG governed the abovementioned processes. The thin film exhibited an R3c phase and enhanced Bi-O-Fe coordination as compared to the sub-5 nm nanoparticles. Raman spectroscopy under the influence of a magnetic field shows a magnetoelectric effect, spin phonon coupling, and magnetic anisotropy. We report room-temperature ferroelectric behavior in the thin film, which enhances with the application of a magnetic field; this confirms the multiferroic nature of the thin film. The thin film shows polarization switching ability at multiple voltages and read-write operation at low bias (±0.5 V). Furthermore, the thin film shows negative differential-complementary resistive switching behavior in the nano-microampere current range. We report nearly stable 1-bit operation for 102 cycles, 105 voltage pulses, and 105 s, demonstrating the paradigm device applications. The observed results thus show that the thin films prepared using sub-5 nm BiFeO3 nanoparticles are a promising candidate for future spintronics and memory applications. The reported approach can also be pertinent to explore the physicochemical properties and develop potential applications of several other nanoparticles.