Anti-hepatocellular carcinoma activity of Sorbaria sorbifolia by regulating VEGFR and c-Met/apoptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorbaria sorbifolia (SS) is a traditional Chinese medicine (TCM) that has been employed anti-hepatocellular carcinoma (HCC) for over 2000 years; yet, its underlying mechanism is still not fully understood. AIM OF THE STUDY: In this study, we evaluated the anti-HCC effect on the freeze-dried powder of the water extract of SS (FDSS) by inhibiting tumor-induced neovascularization, and promoting apoptosis, and elucidated the underlying mechanisms. MATERIALS AND METHODS: HCC cell lines (HepG2 and Huh7 cells) and HepG2 xenograft tumors in zebrafish were employed as in vivo and in vitro models, respectively, to evaluate the anti- HCC-indued neovascularization and apoptosis. In HCC cell lines, CCK-8 assay, wound-healing assay, transwell assay, cell circle assay, apoptosis assay, transmission electron microscopy, and co-culture assay were performed in vitro; in HepG2 xenograft tumor-zebrafish, tumor growth inhibition assay, hematoxylin and eosin (HE) staining, xenograft tumor-zebrafish apoptosis assay, and HCC-indued neovascularization assay were performed to evaluate the effect of FDSS on biological behavior of tumor, HCC-indued neovascularization, and apoptosis. The expression of VEGFR and c-Met/apoptotic pathway-related proteins was detected by western blotting analysis. Assays for c-Met and VEGFR activation were conducted to assess the impact of FDSS in either agonistic or inhibitory roles on these receptor proteins. RESULTS: The findings from our study revealed that FDSS effectively suppresses the proliferation, migration, and invasion of HepG2 and Huh7 cells, as well as inhibiting tumor growth in the HepG2 xenograft zebrafish model by downregulating the expression of p-Met and p-AKT proteins. FDSS decreased the tumor growth associated with promoting apoptosis, including arresting HepG2 and Huh7 cells cycle at G0/G1phase, increasing apoptotic cell numbers and apoptotic bodies in cancer cells, and increasing the apoptotic fluorescence of xenograft tumor zebrafish by downregulating Bcl-2 proteins and upregulating Bax, caspase-9, and caspase-3 levels. We also found that FDSS can inhibit HCC-induced neovascularization and regulate VEGFR. Using an agonist or inhibitor of c-Met and VEGFR in HepG2 cells, we discovered that FDSS can downregulate c-Met and VEGFR protein expression. CONCLUSION: FDSS exerts an anti-HCC effect by inhibiting HCC-indued neovascularization and pro-apoptosis through the inhibition of the action of VEGFR and c-Met/apoptotic pathway.

Resveratrol promotes skin wound healing by regulating the miR-212/CASP8 axis.

The wound-healing process is a natural response to burn injury. Resveratrol (RES) may have potential as a therapy for wound healing, but how and whether RES regulates skin repair remains poorly understood. Human epidermal keratinocyte (HaCaT) cells were treated with lipopolysaccharide (LPS), and a mouse skin wound-healing model was established. Cell viability and apoptosis were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide or flow cytometry. Cell proliferation was assessed by cell viability and colony-formation analyses. Cell migration was tested by wound-healing analysis. The microRNA-212 (miR-212) and caspase-8 (CASP8) levels were determined by quantitative reverse transcription polymerase chain reaction and western blotting. The correlation between miR-212 and CASP8 was analyzed by dual-luciferase reporter analysis. Skin wound healing in mice was assessed by measuring the wound area and gap after hematoxylin-eosin (HE) staining. RES reduced the LPS-induced reduction in viability and apoptosis in HaCaT cells. miR-212 expression was reduced by LPS and increased by exposure to RES. RES promoted cell proliferation and migration after LPS treatment by increasing miR-212 levels. CASP8 was a target of miR-212. CASP8 silencing promoted cell proliferation and migration, which was reversed by miR-212 knockdown in LPS-treated HaCaT cells. RES promoted skin wound healing in mice, which was reduced by miR-212 knockdown. Thus, RES facilitates cell proliferation and migration in LPS-treated HaCaT cells and promotes skin wound-healing in a mouse model by regulating the miR-212/CASP8 axis.

Production of an Animal Model of Semi-Yin and Semi-Yang Syndrome with Diabetic Ulcers and Study of Its Pathological and Metabolic Features.

BACKGROUND: To create an animal model for diabetic ulcers with semi-Yin and semi-Yang (SYSY) syndrome and to study the pathological and metabolic features of SYSY syndrome. METHODS: Firstly, based on the clinical characteristics of the SYSY syndrome of diabetic ulcer, an animal model of diabetic ulcers with SYSY syndrome being full-thickness skin defects was created by injecting streptozotocin (STZ) intraperitoneally, infecting with Staphylococcus aureus, and gastrically administering senna. Secondly, the content and distribution patterns of collagen fibers, the expression of neutrophils and macrophage markers, angiogenesis, and the expression of IL-1ß and IL-10 in the rats with Yang syndrome, Yin syndrome, and SYSY syndrome of diabetic ulcers at different time points were detected. Representative traditional Chinese medicine (TCM) ointment of Yang syndrome, Yin syndrome, and SYSY syndrome was used to treat this animal model. The above indexes in each treatment group were detected. Finally, metabonomics was used to detect and analyze the changes of differential metabolites related to macrophage metabolism in Yang, Yin, and SYSY syndromes at different time points. RESULTS: An animal model of diabetic ulcers with SYSY syndrome was established. The pathological features of the SYSY syndrome group were chronic low-grade inflammatory reactions. On the third day, the SYSY syndrome group displayed lower expression of CD16, CD68, CD163, IL-1ß, and metabolites related to M1-type macrophages compared with other groups. On the seventh day, the SYSY syndrome group showed lower expression of CD31, IL-10, myeloperoxidase, and metabolites related to M2-type macrophages. Treatment with Chong He Ointment, a representative TCM ointment for SYSY syndrome, reversed the expression levels of these indexes and promoted wound healing in the SYSY group. CONCLUSION: SYSY syndrome presents a persistent pathological state of low inflammation, which may be caused by an insufficient activation of the M1-type metabolic pathway in macrophages in the early acute inflammatory stage, resulting in the incomplete clearance of pathogens and debris and continuous stimulation of macrophages to initiate the M1-type metabolic pathway. CD163, CD31, IL-10, and citric acid can be used as potential specific markers for the recovery and progression of SYSY syndrome.

Identification of immune-related genes as prognostic factors in bladder cancer.

Bladder cancer is one of the most common cancers worldwide. The immune response and immune cell infiltration play crucial roles in tumour progression. Immunotherapy has delivered breakthrough achievements in the past decade in bladder cancer. Differentially expressed genes and immune-related genes (DEIRGs) were identified by using the edgeR package. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for functional enrichment analysis of DEIRGs. Survival-associated IRGs were identified by univariate Cox regression analysis. A prognostic model was established by univariate COX regression analysis, and verified by a validation prognostic model based on the GEO database. Patients were divided into high-risk and low-risk groups based on the median risk score value for immune cell infiltration and clinicopathological analyses. A regulatory network of survival-associated IRGs and potential transcription factors was constructed to investigate the potential regulatory mechanisms of survival-associated IRGs. Nomogram and ROC curve to verify the accuracy of the model. Quantitative real-time PCR was performed to validate the expression of relevant key genes in the prognostic model. A total of 259 differentially expressed IRGs were identified in the present study. KEGG pathway analysis of IRGs showed that the "cytokine-cytokine receptor interaction" pathway was the most significantly enriched pathway. Thirteen survival-associated IRGs were selected to establish a prognostic index for bladder cancer. In both TCGA prognostic model and GEO validation model, patients with high riskscore had worse prognosis compared to low riskscore group. A high infiltration level of macrophages was observed in high-risk patients. OGN, ELN, ANXA6, ILK and TGFB3 were identified as hub survival-associated IRGs in the network. EBF1, WWTR1, GATA6, MYH11, and MEF2C were involved in the transcriptional regulation of these survival-associated hub IRGs. The present study identified several survival-associated IRGs of clinical significance and established a prognostic index for bladder cancer outcome evaluation for the first time.

Assessing the prognostic value of stemness-related genes in breast cancer patients.

Breast cancer (BC) is currently one of the deadliest tumors worldwide. Cancer stem cells (CSCs) are a small group of tumor cells with self-renewal and differentiation abilities and high treatment resistance. One of the reasons for treatment failures is the inability to completely eliminate tumor stem cells. By using the edgeR package, we identified stemness-related differentially expressed genes in GSE69280. Via Lasso-penalized Cox regression analysis and univariate Cox regression analysis, survival genes were screened out to construct a prognostic model. Via nomograms and ROC curves, we verified the accuracy of the prognostic model. We selected 4 genes (PSMB9, CXCL13, NPR3, and CDKN2C) to establish a prognostic model from TCGA data and a validation model from GSE24450 data. We found that the low-risk score group had better OS than the high-risk score group, whether using TCGA or GSE24450 data. A prognostic model including four stemness-related genes was constructed in our study to determine targets of breast cancer stem cells (BCSCs) and improve the treatment effect.

Prognostic value of immune related genes in lung adenocarcinoma.

Lung cancer has the highest incidence and mortality rates of all cancers in China. Immune-related genes and immune infiltrating lymphocytes are involved in tumor growth, and in the past decade, immunotherapy has become increasingly important in the treatment of lung cancer. Using the edgeR package, differentially expressed genes and immune-related genes (DEIRGs) were identified in patients with lung adenocarcinoma (LUAD). Functional enrichment analysis of DEIRGs was performed using Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Survival-associated immune-related genes (IRGs) were selected using univariate Cox regression analysis and the prognostic model was assessed using multivariate Cox regression analysis. Overall, 273 DEIRGs were identified in LUAD, and KEGG pathway analysis of IRGs showed that 'cytokine-cytokine receptor interaction' was the most significantly enriched pathway. Furthermore, six survival associated IRGs were screened to establish a prognostic model; patients in the high risk score group had less favorable survival times, and the prognostic model was negatively associated with B cell infiltration. The present study established a prognostic model using analysis of survival-related immune-related genes, which were associated with B cell infiltration.

Combined PLT and NE to predict the prognosis of patients with locally advanced cervical cancer.

Cervical cancer is one of the most common tumors in women. Neutrophils (NEs) and platelets (PLTs) are components of cells in circulating blood. NEs are one of the components of white blood cells (WBCs), accounting for the vast majority of WBCs, recognized as one of the indicators of inflammation. PLTs are associated with thrombosis and inflammation. Both of them play an important role in tumor growth and metastasis. According to pre-radiotherapy PLT and NE media levels, we divided the patients into three groups: PLT and NE both high levels group, single high level group and both low group. By using COX regression models and nomogram, a prognostic model for patients was established. Both high levels of pre-radiotherapy PLT and NE group or high levels of post-radiotherapy PLT and NE group were correlated with worst overall survival (OS) compared with the other two groups. PLT and NE were correlated with outcomes of the patients with locally advanced cervical cancer.

Prognostic Values of LDH and CRP in Cervical Cancer.

PURPOSE: Cervical cancer is one of the deadliest tumors among women in China. C-reactive protein (CRP), an indicator of inflammation, and lactate dehydrogenase (LDH), an enzyme ubiquitously expressed in cells, both play important roles in tumor growth and metastasis. PATIENTS AND METHODS: Based on pre-radiotherapy LDH and CRP median levels, we divided patients into four groups: high LDH and CRP group, high LDH group, high CRP group, and low LDH and CRP group. Then, based on pre-/post-radiotherapy LDH and CRP ratios, we divided patients into four groups: high LDH and CRP ratio group, high LDH ratio group, high CRP ratio group, and low LDH and CRP ratio group. Kaplan-Meier (KM) curves were constructed to show overall survival (OS). A multivariate Cox regression model was employed to identify the independent risk factors. RESULTS: High pre-radiotherapy LDH and CRP levels and increased pre-/post-radiotherapy LDH and CRP ratios were correlated with worst OS compared with the other three groups. CONCLUSION: LDH and CRP were correlated with outcomes in patients with locally advanced cervical cancer.

Prognostic values of lymphocyte and eosinophil counts in resectable cervical squamous cell carcinoma.

Aim: Cervical cancer is one of the leading causes of cancer mortality in women. Peripheral white blood cell parameters such as neutrophil (NE), eosinophil (EO), basophil (BA), as well as lymphocyte (LY) and monocyte (MO), are correlated with tumor outcomes. Methods: In total, 110 cervical squamous cell carcinoma patients were recruited in this study. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. Results: Cox regression analysis model indicated that higher pretreatment EO level and increased post-/preradiotherapy EO ratio were independently associated with worse progression-free survival. Lower pretreatment LY or higher EO levels and increased post-/preradiotherapy EO ratio were independently associated with worse overall survival. Conclusion: LY and EO are correlated with outcomes of cervical squamous cell cancer.

Prognostic Values of Platelet-Associated Indicators in Resectable Cervical Cancer.

BACKGROUND: Cervical cancer is one of the leading causes of cancer mortality in women, which seriously threatens the health of women worldwide. Platelet (PLT)-related parameters, including PLT count, mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW), are correlated with tumor prognosis. METHODS: In total, 110 patients with cervical carcinoma were recruited in this study. The patients were divided into 2 groups according to the receiver operating characteristic analysis cutoff values of PLT, MPV, PCT, or PDW. The post-/preradiotherapy ratios were defined as the rate of preradiotherapy PLT-related parameters counts and the corresponding ones obtained after radiotherapy. RESULTS: Higher pretreatment PLT level was correlated with Higher Federation of Gynecology and Obstetrics (FIGO) stage (II). Higher pretreatment PLT level was correlated with worse progression-free survival (PFS) and overall survival (OS). Increased post-/preradiotherapy ratio of PLT was correlated with worse PFS and OS. Changes in PCT, MPV, or PDW levels had no effects on PFS or OS. Cox regression analysis model indicated that larger tumor size, higher pretreatment PLT level, and increased post-/preradiotherapy PLT ratio were independently associated with worse PFS; higher FIGO stage (II) and increased post-/preradiotherapy PLT ratio were independently associated with worse OS. CONCLUSION: Pretreatment PLT level and increased post-/preradiotherapy PLT ratio are correlated with outcomes of cervical cancer.

Design and biomechanical characteristics of porous meniscal implant structures using triply periodic minimal surfaces.

BACKGROUND: Artificial meniscal implants can be used to replace a severely injured meniscus after meniscectomy and restore the normal functionality of a knee joint. The aim of this paper was to design porous meniscal implants and assess their biomechanical properties. METHODS: Finite element simulations were conducted on eight different cases including intact healthy knees, knee joints with solid meniscal implants, and knee joints with meniscal implants with two types of triply periodic minimal surfaces. Compression stresses, shear stresses, and characteristics of stress concentrated areas were evaluated using an axial compressive load of 1150 N and an anterior load of 350 N. RESULTS: Compared to the solid meniscal implant, the proposed porous meniscal implant produced lower levels of compression and shear stresses on the cartilage, which facilitated the cartilage to retain a semilunar characteristic similar to the natural meniscus. Moreover, both compression and shear stresses on the artificial cartilage were found to be sensitive to the pore properties of the meniscal implant. The meniscal implants with primitive surfaces (porosity: 41%) showed a better performance in disseminating stresses within the knee joint. CONCLUSION: The present commercial meniscal implant has the problem of equivalent biomechanical properties compared to natural menisci. The main advantage of the proposed porous structure is that it can be used to prevent excessive compression and shear stresses on the articular cartilages. This structure has advantages both in terms of mechanics and printability, which can be beneficial for future clinical applications.

Prognostic Values of Systemic Inflammation Response (SIR) Parameters in Resectable Cervical Cancer.

BACKGROUND: Cervical carcinoma is the leading cause of cancer mortality in women. C-reactive protein (CRP), albumin (ALB), globulin (GLB), lactate dehydrogenase (LDH), and albumin-to-globulin ratio (AGR) are indicators of systemic inflammation response correlated with tumor outcomes. METHODS: This study recruited 110 patients with cervical cancer. The patients were divided into 2 groups according to pretreatment median values of CRP, ALB, GLB, LDH, and AGR. The post/preradiotherapy or post/pretreatment ratios were defined as rates of pretreatment CRP, ALB, GLB, LDH, and AGR values and the corresponding ones obtained after radiotherapy or whole treatment. RESULTS: Higher pretreatment CRP or LDH levels were correlated with worse progression-free survival (PFS) and overall survival (OS). Increased post/preradiotherapy CRP ratio was correlated with worse PFS and OS, increased post/preradiotherapy LDH ratio was correlated with worse PFS. Increased post/pretreatment CRP ratio was correlated with worse PFS and OS, not-increased post/pretreatment AGR ratio was correlated with worse OS. Cox regression analysis model indicated that, moderately or poorly of differentiation, higher pretreatment CRP or LDH levels were independently associated with worse PFS, higher pretreatment CRP or LDH levels and increased post/pretreatment CRP ratio were independently associated with worse OS. CONCLUSION: CRP, LDH, or AGR are correlated with outcomes of resectable cervical cancer.

A new species of genus Thoradonta Hancock, 1908 (Orthoptera: Tetrigoidea: Tetrigidae) from India.

A new species of genus Thoradonta subtruncata sp. nov. is described from Korba, Chhattisgarh, India. A brief comparison with the reference collection Thoradonta spiculoba Hancock, 1912 present in National Zoological Collection identified by Prof. K. K. Günther. The new species Thoradonta subtruncata sp. nov. is similar to Thoradonta spiculoba Hancock, 1912, but differs from latter by median carina of vertex distinct and elevated, facial carinae slightly sinuated between antennae, scutellum moderate near median ocellus, tegmen elongate, more punctuate, narrow in middle, apex subtruncate and pulvilli III distinctly longer than length of I and II pulvilli.

A new species of the genus Humphaplotropis from China (Orthoptera: Pamphagidae, Pamphaginae).

A new species of the genus Humphaplotropis Xiao et al, 2013, i.e. Humphaplotropis tongbaishanensis sp. nov. is described from Henan province, China in this paper. The new species is allied Humphaplotropis xiai Zhi, Shi Dai, 2015, but differs from latter by tegmina of male short, not reaching the hind margin of 1st abdominal tergite; base of cercus not narrow in male; epiphallus with disperse spikes, ancorae broad, both posterior projections shorter than median projection; length of subgenital plate larger than width in female and Krauss` organ of female with 20 keels. The genus Humphaplotropis Xiao et al, 2013 is a valid genus and not a synonym of Haplotropis Saussure, 1888. Type specimens are deposited in Shanghai Entomological Museum, C.A.S., Shanghai China.

A new species of the genus Xya Latreille, 1809 from China (Orthoptra, Tridctyloidea, Tridactylidae).

A new species of the genus Xya Latreille, 1809 from Sichuan, China is described in this paper. The new species Xya sichuanensis sp. nov. is similar to Xya japonica (Haan, 1844), but differs from latter by head with yellow stripe on both sides, vertex with two yellow stripes on the inner margin of eyes, pronotum with yellow stripe on both sides, tegmina with two small yellow spots, fore and mid legs black, with yellow spots and hind wing yellow. Type specimens are deposited in the College of Life Science, Leshan Normal University, Leshan 614004, China.

Description of a new species of the genus Mongolotettix Rehn, 1928 (Orthoptera: Acrididae) from Fujian, China.

A new species of the genus Mongolotettix Rehn, 1928 from Fujian, China is described in this paper. The new species Mongolotettix.fujianensis sp. nov. is similar to M. wulingyuanensis Shi, Liu et Li, 2016, but differs from the latter by maximum width of cubital area 1.4 times maximum width of medial area in tegmina of male; body small, length of body ♂ 21.5. mm, ♀ 30.6 mm; vertical diameter eye 1.3 times horizontal diameter in male; hind femur of male with 103 stridulatory pegs on inner side and epiphallus with indistinct projection on inner side of lateral plates. Type specimens are deposited in the Shanghai Entomological Museum, Chinese Academy of Sciences, Shanghai, 200032, China.

A new species of the genus Tridactylus Olivier, 1789 (Orthoptera, Tridactyloidea, Tridactylidae) from India.

A new species of genus Tridactylus bijakherensis sp. nov. is described from Korba, Chhattisgarh, India, with a key to the Indian species of the genus Tridactylus Olivier, 1789.

Mechanical characterization of 3D printed multi-morphology porous Ti6Al4V scaffolds based on triply periodic minimal surface architectures.

Heterogeneous biomaterials that simultaneously mimic the topological and mechanical properties of nature bone tissues are of great interest in recent years. In this study, multi-morphology porous scaffolds based on the triply periodic minimal surfaces (TPMS) were designed and 3D printed with spatially changing pore patterns. Experiments and numerical analyses were carried out to assess the mechanical properties of the multi-morphology graded porous scaffold. As can be seen from the results, the multi-morphology structure showed a combination of relatively low elastic moduli and high yield strength. This combination allows for simultaneously minimizing the bone damage and increasing the stability of bone-implant interface. Thus the 3D printed multi-morphology porous Ti6AlV scaffold had shown significant promise for orthopedic application.

Two new species of the genus Sinopodisma Chang, 1940 (Orthoptra, Acridoidea, Catantopidae, Podisminae) from Taiwan, China.

Two new species of the genus Sinopodisma Chang, 1940 from Taiwan, China are described in this paper. The new species Sinopodisma orchofemura sp. nov. is similar to Sinopodisma kodamae (Shiraki, 1910), but differs from latter in antennae length of joint 2.9 times width in the middle part, hind femur yellow, length of interspace of mesosternum larger than narrowest, tegmina almost reaching the hind margin of second abdominal tergum. The Sinopodisma hsinchuensis sp. nov. is similar to Sinopodisma orchofemura sp. nov., but differs from latter by vertical diameter of eyes 1.7 times horizontal diameter and 1.8 times subocular furrow; tegmina extending over the hind margin of first abdominal tergite slightly; the length of interspace of mesosternum equal to narrowest and subgenital plate longer than ovipositor valves ventral view. Type specimens are deposited in the National Museum of Natural Science, Taichung, Taiwan, China and the Institute of Entomology, Taiwan University, Taibei, Taiwan, China respectively.

A new species of the genus Mongolotettix Rehn, 1928 from Hubei, China (Acrididae, Acridoidea, Orthoptera).

The genus Mongolotettix Rehn, 1928 is a small genus of family Adrididae. It has nine species discovered from the Far Eastern Asian countries, including China, Japan, Korea, Mongolia, and Russia [Bolívar, 1898; Uvarov, 1914; Caudell, 1921; Chogsomzhav, 1974; Li et Lian, 1994; Wan, Ren et Zhang, 1998; Xie et Li, 2000, Kim et Kim 2005; Dong, et al, 2015; Shi et al, 2016; Storozhenko, 2016; Eades et al, 2017; Zhang et al, 2017]. In the present paper, we describe a new species of the genus from Hubei, China. Type specimens are deposited in the College of Plant Protection, Shandong Agricultural University, Taian, Shandong, China.