PSIP1 promotes gefitinib resistance in lung adenocarcinoma by inducing the expression of WASF3 and its downstream ITGB3/AKT signaling.

BACKGROUND: Gefitinib (GR), a representative drug of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is a key pillar in the treatment of lung adenocarcinoma (LUAD), but drug resistance is universal. Identifying the potential factors of drug resistance to GR is essential to treat patients with EGFR mutant LUAD. METHODS: The GR-resistant LUAD cells were established and confirmed by MTT assay. The effects of PC4 and SRSF1 interacting protein 1 (PSIP1) on GR-resistant cell proliferation and apoptosis in vitro and in vivo were detected by colony formation, flow cytometry, tumor-bearing animal model, immunohistochemistry, and TUNEL staining. Western blotting and qPCR were used to determine the expression of relevant markers. The effect of PSIP1 on the promoter region of Wiskott-Aldrich syndrome protein family member 3 (WASF3) was detected by the dual-luciferase assay. The interaction between PSIP1 and RNA polymerase II was evaluated using ChIP-qPCR and Co-IP assays. RESULTS: PSIP1 was highly enriched in GR-resistant LUAD cells. Downregulation of PSIP1 expression significantly inhibited the proliferation of LUAD-resistant cells and promoted apoptosis. WASF3 was shown to have similar effects as PSIP1 in promoting drug resistance in LUAD cells. PSIP1 promoted the transcriptional activity of WASF3, which was achieved by increasing RNA polymerase II recruitment on the WASF3 promoter. Furthermore, PSIP1 positively regulated the expression of the pro-EGFR-TKI resistance factor integrin subunit beta 3 (ITGB3). CONCLUSION: Our work suggests that PSIP1 promotes resistance to GR in LUAD cells by inducing the expression of WASF3 and its downstream regulator ITGB3.

Sinonasal/basicranial myxofibrosarcoma: a report of 6 surgical cases combined with a literature review

Abstract Objective: The aim of this study was to report 6 cases of sinonasal/basicranial myxofibrosarcoma and review demographic data, clinical symptoms, diagnostic methods, therapeutic methods, and prognosis on this subject in the literature. Methods: We conducted a retrospective analysis of six patients referred to our hospital during a 10-year period from 2010 to 2020. Results: In this series, there were four males and two females. The tumours originated from the maxillary sinus in all six cases. The symptoms were nonspecific, and all patients underwent endoscopic resection alone or combined with open resection. The postoperative period was uneventful. All patients were diagnosed with myxofibrosarcoma. After a median follow-up period of 36 (6-52) months, the recurrence rate of MFS was 66.7% (4/6), and the mortality rate was 50% (3/6). Conclusion: Sinonasal/basicranial MFS is a rare neoplasm, and the most common primary site is the maxillary sinus. When diagnosing MFS, osteolysis may help rule out benign lesions. So far surgery is the mainstay of treatment for sinonasal/basicranial MFS. Our surgical strategy using endoscopic resection or endoscopic resection combined with open resection to achieve a negative surgical margin and using re-excision operations to treat relapsed cases may be recommended to rhinologists who treat MFS. Prospective randomised trials are needed to study the role of chemotherapy, radiotherapy, and our surgical strategy for sinonasal/basicranial MFS. Diagnosing patients at an earlier stage and better patient compliance with follow-up plans may improve the prognosis of patients.

Sinonasal/basicranial myxofibrosarcoma: a report of 6 surgical cases combined with a literature review.

OBJECTIVE: The aim of this study was to report 6 cases of sinonasal/basicranial myxofibrosarcoma and review demographic data, clinical symptoms, diagnostic methods, therapeutic methods, and prognosis on this subject in the literature. METHODS: We conducted a retrospective analysis of six patients referred to our hospital during a 10-year period from 2010 to 2020. RESULTS: In this series, there were four males and two females. The tumours originated from the maxillary sinus in all six cases. The symptoms were nonspecific, and all patients underwent endoscopic resection alone or combined with open resection. The postoperative period was uneventful. All patients were diagnosed with myxofibrosarcoma. After a median follow-up period of 36 (6-52) months, the recurrence rate of MFS was 66.7% (4/6), and the mortality rate was 50% (3/6). CONCLUSION: Sinonasal/basicranial MFS is a rare neoplasm, and the most common primary site is the maxillary sinus. When diagnosing MFS, osteolysis may help rule out benign lesions. So far surgery is the mainstay of treatment for sinonasal/basicranial MFS. Our surgical strategy using endoscopic resection or endoscopic resection combined with open resection to achieve a negative surgical margin and using re-excision operations to treat relapsed cases may be recommended to rhinologists who treat MFS. Prospective randomised trials are needed to study the role of chemotherapy, radiotherapy, and our surgical strategy for sinonasal/basicranial MFS. Diagnosing patients at an earlier stage and better patient compliance with follow-up plans may improve the prognosis of patients.

Novel 4-phenoxypyridine derivatives bearing imidazole-4-carboxamide and 1,2,4-triazole-3-carboxamide moieties: Design, synthesis and biological evaluation as potent antitumor agents.

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC50 value of 0.012 µM) showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines with IC50 values of 0.64 µM, 1.92 µM and 2.68 µM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that imidazole-4-carboxamide was more preferred as linker part, and electron-withdrawing groups (especially halogen groups) on the terminal phenyl rings were beneficial for improving the antitumor activities.

Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer.

BACKGROUND: Kidney cancer is one of the most common cancers in the world. It is necessary to clarify its underlying mechanism and find its prognostic biomarkers. Current studies showed that SHMT2 may be participated in several kinds of cancer. METHODS: Our studies investigated the expression of SHMT2 in kidney cancer by Oncomine, Human Protein Atlas database and ULCAN database. Meanwhile, we found its co-expression gene by cBioPortal online tool and validated their relationship in A498 and ACHN cells by cell transfection, western blot and qRT-PCR. Besides these, we also explored their prognostic values via the Kaplan-Meier plotter database in different types of kidney cancer patients. RESULTS: SHMT2 was found to be increased in 7 kidney cancer datasets, compared to normal renal tissues. For the cancer stages, ages and races, there existed significant difference in the expression of SHMT2 among different groups by mining of the UALCAN database. High SHMT2 expression is associated with poor overall survival in patients with kidney cancer. Among all co-expressed genes, NDUFA4L2 and SHMT2 had a high co-expression efficient. SHMT2 overexpression led to the increased expression of NDUFA4L2 at both mRNA and protein levels. Like SHMT2, overexpressed NDUFA4L2 also was associated with worse overall survival in patients with kidney cancer. CONCLUSION: Based on above results, overexpressed SHMT2 and its co-expressed gene NDUFA4L2 were all correlated with the prognosis in kidney cancer. The present study might be benefit for better understanding the clinical significance of SHMT2 and provided a potential therapeutic target for kidney cancer in future.

Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer

BACKGROUND: Kidney cancer is one of the most common cancers in the world. It is necessary to clarify its underlying mechanism and find its prognostic biomarkers. Current studies showed that SHMT2 may be participated in several kinds of cancer. METHODS: Our studies investigated the expression of SHMT2 in kidney cancer by Oncomine, Human Protein Atlas database and ULCAN database. Meanwhile, we found its co-expression gene by cBioPortal online tool and validated their relationship in A498 and ACHN cells by cell transfection, western blot and qRT-PCR. Besides these, we also explored their prognostic values via the Kaplan-Meier plotter database in different types of kidney cancer patients. RESULTS: SHMT2 was found to be increased in 7 kidney cancer datasets, compared to normal renal tissues. For the cancer stages, ages and races, there existed significant difference in the expression of SHMT2 among different groups by mining of the UALCAN database. High SHMT2 expression is associated with poor overall survival in patients with kidney cancer. Among all co-expressed genes, NDUFA4L2 and SHMT2 had a high co-expression efficient. SHMT2 overexpression led to the increased expression of NDUFA4L2 at both mRNA and protein levels. Like SHMT2, overexpressed NDUFA4L2 also was associated with worse overall survival in patients with kidney cancer. CONCLUSION: Based on above results, overexpressed SHMT2 and its co-expressed gene NDUFA4L2 were all correlated with the prognosis in kidney cancer. The present study might be benefit for better understanding the clinical significance of SHMT2 and provided a potential therapeutic target for kidney cancer in future.

Astilbin reduces ROS accumulation and VEGF expression through Nrf2 in psoriasis-like skin disease.

BACKGROUND: Psoriasis is a common and intractable skin disease affecting the physical and mental health of patients. The accumulation of ROS is involved in the pathogenesis of psoriasis and antioxidants are believed to be therapeutic. This study aimed to investigate the therapeutic efficacy of astilbin on ROS accumulation in psoriasis. RESULTS: The study showed that 50 µg/ml astilbin could inhibit the growth and reduce the accumulation of ROS in HaCaT cells stimulated by IL-17 and TNF-α. Astilbin could elevate the Nrf2 accumulation in the nuclei, eventually leading to the transcriptional activation of various antioxidant proteins and reducing the expression of VEGF. CONCLUSIONS: Our results collectively suggest that astilbin could induce Nrf2 nucleus translocation, which is contribute to reduce the ROS accumulation and VEGF expression, and inhibit the proliferation of HaCaT cells.

Commercial vaccine against pseudorabies virus: A hidden health risk for dogs.

Pseudorabies virus (PRV) is considered as an infectious agent with a wide of host range, causing considerable economic losses in animal husbandry. Although the commercial vaccine against PRV plays an critical role in control of this disease in swine industry, the potential risk of commercial vaccines against PRV for other host is unclear. Here, we report that the commercial vaccine against PRV is a hidden health risk for dogs. We found that different attenuated PRV strains in commercial vaccines possess different tissue tropism, and that the attenuated PRV strains are lethal to dogs, and that the attenuated PRV strain possesses the ability to spread horizontally among the dogs. Collectively, our findings provide clues that the commercial vaccine against PRV is a hidden risk for dogs, even for the owner of pet dogs to take seriously.

Analysis of culturable microbiota present in the stomach of children with gastric symptoms.

Despite extensive studies on the gastric microbiota, including Helicobacter pylori and non-H. pylori, the bacterial composition in children remains unknown. In this study, we analyzed the culturable gastric bacteria in stomach biopsies from 346 children aged 1-15 years affected by gastric diseases. H. pylori and non-H. pylori were identified by specific PCR and 16S rDNA sequencing, respectively. Antibiotic susceptibilities of H. pylori and non-H. pylori were tested by the E-test and disk diffusion methods, respectively. Rapid diagnosis was also performed by H. pylori-specific PCR. Twenty-two H. pylori strains were obtained from culture, and 92 biopsies were positive by H. pylori-specific PCR. The positive rate was higher in boys (40.3%) than in girls (23.3%) (P = 0.001). Resistance rates of 22 H. pylori strains were as follows: metronidazole, 86.4%; tetracycline, 22.7%; amoxicillin, 22.7%; levofloxacin, 31.8%; clarithromycin, 36.4%. Ten isolates were multidrug-resistant. Additionally, among 366 non-H. pylori strains, 204 exhibited urease activity. Non-H. pylori resistance rates were as follows: metronidazole, 94.8%; tetracycline, 26.2%; amoxicillin, 42.6%; levofloxacin, 15.3%; clarithromycin, 46.7%. Our results showed that children with gastric disorders harbor stomach bacteria with urease activity or nitrate reductase activity. Further studies will determine the effects of non-H. pylori bacteria in gastric diseases.

Astilbin reduces ROS accumulation and VEGF expression through Nrf2 in psoriasis-like skin disease

Background: Psoriasis is a common and intractable skin disease affecting the physical and mental health of patients. The accumulation of ROS is involved in the pathogenesis of psoriasis and antioxidants are believed to be therapeutic. This study aimed to investigate the therapeutic efficacy of astilbin on ROS accumulation in psoriasis. Results: The study showed that 50 μg/ml astilbin could inhibit the growth and reduce the accumulation of ROS in HaCaT cells stimulated by IL-17 and TNF-α. Astilbin could elevate the Nrf2 accumulation in the nuclei, eventually leading to the transcriptional activation of various antioxidant proteins and reducing the expression of VEGF. Conclusions: Our results collectively suggest that astilbin could induce Nrf2 nucleus translocation, which is contribute to reduce the ROS accumulation and VEGF expression, and inhibit the proliferation of HaCaT cells.

Peratrial Device Closure of Atrial Septal Defect Under Transesophageal Echocardiographic Guidance without Fluoroscopy Compared to Conventional On-Pump Surgical Closure.

Objective: This study is designed to evaluate the advantages between peratrial device closure under transesophageal echocardiographic guidance and open heart surgery in atrial septal defect. Methods: From November 2011 to September 2014, 28 patients with atrial septal defect were treated. Fourteen patients received peratrial device closure under transesophageal echocardiographic guidance (TEE group) and 14 patients received cardiopulmonary bypass (CPB group). Clinical parameters during intraoperative and postoperative periods were examined. Results: All patients recovered after surgery without serious complications. Compared with that in CPB group, clinical observations in TEE group showed significant decreases in the operation time (193.6±35.5 vs. 77.4±22.7 min, P<0.05), periods in intensive care unit (31.6±23.3 vs. 17.5±8.1 hours, P<0.05), fluid volume after operation (502.5±439.3 vs. 32.5±7.3 ml, P<0.05), postoperative length of hospital stay (8.9±2.8 vs. 6.8±2.4 days, P<0.05) and total hospitalization cost (7205.9±1617.6 vs. 5882.3±441.2 $, P<0.05). Conclusion: The peratrial device closure of atrial septal defect under transesophageal echocardiographic guidance is a mini-invasive, simple, safe and effective intervention. Its use in the clinical practice should be encouraged.

Peratrial device closure of atrial septal defect under transesophageal echocardiographic guidance without fluoroscopy compared to conventional on-pump surgical closure

Abstract Objective: This study is designed to evaluate the advantages between peratrial device closure under transesophageal echocardiographic guidance and open heart surgery in atrial septal defect. Methods: From November 2011 to September 2014, 28 patients with atrial septal defect were treated. Fourteen patients received peratrial device closure under transesophageal echocardiographic guidance (TEE group) and 14 patients received cardiopulmonary bypass (CPB group). Clinical parameters during intraoperative and postoperative periods were examined. Results: All patients recovered after surgery without serious complications. Compared with that in CPB group, clinical observations in TEE group showed significant decreases in the operation time (193.6±35.5 vs. 77.4±22.7 min, P<0.05), periods in intensive care unit (31.6±23.3 vs. 17.5±8.1 hours, P<0.05), fluid volume after operation (502.5±439.3 vs. 32.5±7.3 ml, P<0.05), postoperative length of hospital stay (8.9±2.8 vs. 6.8±2.4 days, P<0.05) and total hospitalization cost (7205.9±1617.6 vs. 5882.3±441.2 $, P<0.05). Conclusion: The peratrial device closure of atrial septal defect under transesophageal echocardiographic guidance is a mini-invasive, simple, safe and effective intervention. Its use in the clinical practice should be encouraged.

Postnatal variation of limb bones in the Japanese quail, Coturnix coturnix japonica / Variación postnatal de huesos de los miembros en la codorniz japonesa, Coturnix coturnix japonica

Changes in body size over ontogeny may influence the ontogenetic development of long bones, and thus important to our understanding of variation in morphological, physiological, and life-history traits within species. In this study, we sample the entire measurements of the Japanese quail (Coturnix coturnix japonica) of individual skeletons, to investigate the ontogenetic allometry of limb bone proportions by Reduced Major Axis (RMA) regression. The ulna and humerus were both positively allometric in relation to body mass, with their proximal ends growth more rapidly than other regions. Hindlimb bones exhibited more than one allometric pattern. The tarsometatarsus was negative; the femur presented positive allometry, with the width and depth of the proximal end scaled more strongly; measurements of the tibiotarsus were dominated by more rapid growth, especially the width of the proximal end. The growth patterns are suggested to be correlated with the ontogeny of behavior, and reflect the muscular requirements for different mode of locomotion.

Los cambios en el tamaño corporal sobre la ontogenia pueden influir en el desarrollo ontogenético de los huesos largos, y por lo tanto es importante conocer la variación en sus rasgos morfológicos, fisiológicos y la historia de vida dentro de las especies. En este estudio, se muestran las mediciones completas de esqueletos individuales de codorniz japonesa (Coturnix coturnix japonica), para investigar la alometría ontogenética de las proporciones de los huesos de los miembros mediante la regresión del Eje Mayor Reducido (RMA). La ulna y el húmero fueron ambos positivos alométricamente en relación a la masa corporal, con un crecimiento más ligero de sus extremos proximales que de otras regiones. Los huesos de los miembros posteriores mostraron más de un patrón alométrico. El tarsometatarsus fue negativo; el fémur presentó alometría positiva, con un ancho y profundidad del extremo proximal importantes. Las mediciones del tibiotarso presentaron un crecimiento más rápido, sobre todo la anchura del extremo proximal. Los patrones de crecimiento sugieren estar correlacionados con la ontogenia de la conducta, y reflejan los requisitos musculares para un modo de locomoción diferente.

Cloning of a novel xylanase gene from a newly isolated Fusarium sp. Q7-31 and its expression in Escherichia coli

A strain of Q7-31 was isolated from Qinghai-Tibet Plateau and was identified as Fusarium sp. based on its morphological characteristics and ITS rDNA gene sequence analysis. It has the highest capacity of degrading cell wall activity compared with other 11 strains. To do research on its xylanase activity of Fusarium sp. Q7-31 while the degrading the rice cell walls, the complete gene xyn8 that encodes endo-1, 4-¥â-xylanase secreted by Fusarium sp. Q7-31 was cloned and sequenced. The coding region of the gene is separated by two introns of 56bp and 55bp. It encodes 230 amino acid residues of a protein with a calculated molecular weight of 25.7 kDa. The animo acids sequence of xyn8 gene has higher similarity with those of family 11 of glycosyl hydrolases reported from other microorganisms. The nature peptide encodeing cDNA was subcloned into pGEX5x-1 expression vector. The recombinant plasmid was expressed in Escherichia coli BL21-CodonPlus (DE3)-RIL, and xylanase activity was measured. The expression fusion protein was identified by SDS-PAGE and Western blotting, a new specific band of about 52kDa was identified when induced by IPTG. Enzyme activity assay verified the recombinants proteins as a xylanase. A maxium activity of 2.34U/ mg, the xylanase had optimal activity at pH 6.0 and temperature 40¨¬C .

Cloning of a novel xylanase gene from a newly isolated Fusarium sp. Q7-31 and its expression in Escherichia coli.

A strain of Q7-31 was isolated from Qinghai-Tibet Plateau and was identified as Fusarium sp. based on its morphological characteristics and ITS rDNA gene sequence analysis. It has the highest capacity of degrading cell wall activity compared with other 11 strains. To do research on its xylanase activity of Fusarium sp. Q7-31 while the degrading the rice cell walls, the complete gene xyn8 that encodes endo-1, 4-ß-xylanase secreted by Fusarium sp. Q7-31 was cloned and sequenced. The coding region of the gene is separated by two introns of 56bp and 55bp. It encodes 230 amino acid residues of a protein with a calculated molecular weight of 25.7 kDa. The animo acids sequence of xyn8 gene has higher similarity with those of family 11 of glycosyl hydrolases reported from other microorganisms. The nature peptide encodeing cDNA was subcloned into pGEX5x-1 expression vector. The recombinant plasmid was expressed in Escherichia coli BL21-CodonPlus (DE3)-RIL, and xylanase activity was measured. The expression fusion protein was identified by SDS-PAGE and Western blotting, a new specific band of about 52kDa was identified when induced by IPTG. Enzyme activity assay verified the recombinants proteins as a xylanase. A maxium activity of 2.34U/ mg, the xylanase had optimal activity at pH 6.0 and temperature 40℃.

Cloning of a novel xylanase gene from a newly isolated Fusarium sp. Q7-31 and its expression in Escherichia coli

A strain of Q7-31 was isolated from Qinghai-Tibet Plateau and was identified as Fusarium sp. based on its morphological characteristics and ITS rDNA gene sequence analysis. It has the highest capacity of degrading cell wall activity compared with other 11 strains. To do research on its xylanase activity of Fusarium sp. Q7-31 while the degrading the rice cell walls, the complete gene xyn8 that encodes endo-1, 4--xylanase secreted by Fusarium sp. Q7-31 was cloned and sequenced. The coding region of the gene is separated by two introns of 56bp and 55bp. It encodes 230 amino acid residues of a protein with a calculated molecular weight of 25.7 kDa. The animo acids sequence of xyn8 gene has higher similarity with those of family 11 of glycosyl hydrolases reported from other microorganisms. The nature peptide encodeing cDNA was subcloned into pGEX5x-1 expression vector. The recombinant plasmid was expressed in Escherichia coli BL21-CodonPlus (DE3)-RIL, and xylanase activity was measured. The expression fusion protein was identified by SDS-PAGE and Western blotting, a new specific band of about 52kDa was identified when induced by IPTG. Enzyme activity assay verified the recombinants proteins as a xylanase. A maxium activity of 2.34U/ mg, the xylanase had optimal activity at pH 6.0 and temperature 40ºC .

Comparative genetic diversity and genetic structure of three chinese silkworm species Bombyx mori L. (Lepidoptera: Bombycidae), Antheraea pernyi Guérin-Meneville and Samia cynthia ricini donovan (Lepidoptera: Saturniidae)

The genetic diversity and genetic structure of three Chinese silkworm species Bombyx mori L., Antheraea pernyi Guérin-Meneville and Samia cynthia ricini Donovan were comparatively assessed based on RAPD markers. At the species level, A. pernyi and B. mori showed high levels of genetic diversity, whereas S. cynthia ricini showed low level of genetic diversity. However, at the strain level, A. pernyi had relatively highest genetic diversity and B. mori had lowest genetic diversity. Analysis of molecular variance (AMOVA) suggested that 60 percent and 72 percent of genetic variation resided within strains in A. pernyi and S. cynthia ricini, respectively, whereas only 16 percent of genetic variation occurred within strains in B. mori. In UPGMA dendrogram, individuals of A. pernyi and B. mori formed the strain-specific genetic clades, whereas those of S. cynthia ricini were distributed in a mixed way. The implications of these results for the conservation and utilization in breeding programs of three silkworm species are discussed.

Comparative genetic diversity and genetic structure of three Chinese silkworm species Bombyx mori L. (Lepidoptera: Bombycidae), Antheraea pernyi Guérin-Meneville and Samia cynthia ricini Donovan (Lepidoptera: Saturniidae).

The genetic diversity and genetic structure of three Chinese silkworm species Bombyx mori L., Antheraea pernyi Guérin-Meneville and Samia cynthia ricini Donovan were comparatively assessed based on RAPD markers. At the species level, A. pernyi and B. mori showed high levels of genetic diversity, whereas S. cynthia ricini showed low level of genetic diversity. However, at the strain level, A. pernyi had relatively highest genetic diversity and B. mori had lowest genetic diversity. Analysis of molecular variance (AMOVA) suggested that 60% and 72% of genetic variation resided within strains in A. pernyi and S. cynthia ricini, respectively, whereas only 16% of genetic variation occurred within strains in B. mori. In UPGMA dendrogram, individuals of A. pernyi and B. mori formed the strain-specific genetic clades, whereas those of S. cynthia ricini were distributed in a mixed way. The implications of these results for the conservation and utilization in breeding programs of three silkworm species are discussed.