Abstract Background: Bivalent freeze-dried neurotoxic (FN) antivenom has been the primary treatment since the 1980s for Taiwan cobra (Naja atra) envenomation in Taiwan. However, envenomation-related wound necrosis is a significant problem after cobra snakebites. In the present study, we analyzed the changes in serum venom concentration before and after antivenom administration to discover their clinical implications and the surgical treatment options for wound necrosis. Methods: The patients were divided into limb swelling and wound necrosis groups. The clinical outcome was that swelling started to subside 12 hours after antivenom treatment in the first group. Serum venom concentrations before and after using antivenoms were measured to assess the antivenom's ability to neutralize the circulating cobra venom. The venom levels in wound wet dressing gauzes, blister fluids, and debrided tissues were also investigated to determine their clinical significance. We also observed the evolutional changes of wound necrosis and chose a better wound debridement timing. Results: We prospectively enrolled 15 Taiwan cobra snakebite patients. Males accounted for most of this study population (n = 11, 73%). The wound necrosis group received more antivenom doses than the limb swelling group (4; IQR:2-6 vs 1; IQR:1-2, p = 0.05), and less records of serum venom concentrations changed before/after antivenom use (p = 0.0079). The necrotic wound site may release venom into circulation and cause more severe envenomation symptoms. Antivenom can efficiently diminish limb swelling in cobra bite patients. However, antivenom cannot reduce wound necrosis. Patients with early debridement of wound necrosis had a better limb outcome, while late or without debridement may have long-term hospital stay and distal limb morbidity. Conclusions: Antivenom can efficiently eliminate the circulating cobra venom in limb swelling patients without wound necrosis. Early debridement of the bite site wound and wet dressing management are suggestions for preventing extended tissue necrosis and hospital stay.

Abstract Scutellarin, a flavonoid compound found in Scutellaria barbata, has been demonstrated to exert anti-cancer properity in a variety of human malignancies. However, its biological significance and underlying mechanism in glioblastoma (GBM) remain ambiguous. Network pharmacology approaches and molecular docking technologies were used to predict the crucial biological processes, candidate targets and signaling pathways of scutellarin against GBM. CCK-8, EdU, and colony formation experiments were performed to determine the effects of scutellarin on cell proliferation. Flow cytometry analysis was utilized to detect apoptosis. Western blot assays were used to measure the expression of proteins associated with EGFR-PI3K-AKT signaling. Through network pharmacology and molecular docking analysis, we found that EGFR might be a potential target and PI3K-AKT signaling might be the key signaling pathway for scutellarin to combat GBM. Scutellarin inhibited cell proliferation and induced apoptosis in a dose-dependent manner. Scutellarin also suppressed the phosphorylation level of EGFR in a dose-dependent manner. Scutellarin inactivated PI3K-AKT signaling by targeting EGFR. Moreover, scutellarin-mediated suppression of cell proliferation and increase of apoptosis was greatly reversed in GBM after overexpressing EGFR. Taken together, scutellarin is a novel inhibitor of EGFR-PI3K-AKT signaling to prevent GBM progression.

Abstract To investigate the effect of polyurea on the protective performance of a steel target plate under the combination of shock wave and fragments, the failure characteristics, damage process and micro mechanism of the polyurea coated steel plates with different coating methods under the combination of explosion shock waves and fragments were analyzed through experiments and numerical simulations. The results showed that single-sided coatings aggravated the damage of target plate when the coating thickness was 2 mm. While the polyurea thickness greater than 4 mm could significantly reduce the damage degree of the steel plate. When the polyurea was coated on the double sides, it would aggravate the damage, no matter how thick the polyurea was. Through microscopic research, it was found that the front coated polyurea was severely ablated by detonation products, which greatly reduce its energy absorption efficiency. The polyurea coated on the back underwent tensile fracture under the influence of tensile stress wave. The breaking of intramolecular hydrogen bond of polyurea was the key to the energy absorption of polyurea.

Abstract In this study, rice protein was used as raw material to explore the effects of γ-irradiation treatment doses (0, 0.5, 1, 2, 3, 5 kGy) on the physicochemical properties of rice protein (particle size, zeta potential, secondary structure, scanning electron microscope microstructure), surface hydrophobicity (H0), thermal stability), functional properties (solubility, water and oil retention, emulsification) and sensory quality. The results show that when the γ-irradiation dose is 2 kGy, the average particle size of rice protein is the smallest, the absolute value of the potential is the highest 33.58 mV, the content of β-sheets in the secondary structure is at least 31.16 ± 0.16, and the content of random curl is at most 14.56 ± 0.06, the surface of the microstructure is rough and the degree of pore depression is the deepest, the highest H0 is 160.45 ± 2.98, the minimum denaturation temperature (Td) and enthalpy (△H) are 70.49 ± 0.05 °C and 1.30 ± 0.01 J/g, which shows that γ-irradiation treatment can be significant affect the physicochemical properties of rice protein. When the irradiation dose is 2 kGy, the highest solubility of rice protein is 69.18 ± 1.07%, and the highest water and oil holding capacity are 5.89 ± 0.08 g/g and 3.45 ± 0.04 g/g, respectively. The highest emulsification activity and emulsification stability are 45.65 ± 1.26 m2/g and 208.33 ± 4.79 min, which shows that γ-irradiation treatment can improve the functional properties of protein. When the irradiation dose was less than 5 kGy, the sensory quality of rice protein was not significantly affected. The research results provide a theoretical basis for the deep processing and value-added utilization of rice protein by γ-irradiation technology.

Abstract Frailty is a geriatric syndrome that predicts the onset of disability, morbidity and mortality in elderly people; it is a state of pre-disability and is reversible. This review aimed to assess the impact of dietary supplementation interventions in frail older adults. A systematic search of PubMed, Web of Science, Embase, and the Cochrane Library databases was performed to collect randomized controlled trials of dietary supplements for the treatment of frailty in the elderly published before March 2022. The frailty score, muscle mass, muscle strength and physical performance of the frail elderly were extracted for analysis. Meta-analysis was performed using Review Manager Version 5.4 and Stata version 15.0. Totally, 18 studies met the inclusion criteria, with 1204 participants (603 experiment group vs. 601 control group). Compared to control group, multi-nutrient nutrition intervention can significantly improve the frailty score of the elderly (MD = -0.19, 95% CI: -0.38 to -0.01, P = 0.04, I2 = 0). Protein supplementation intervention significantly improved body weight (MD = 4.86, 95% CI: 1.21 to 8.52, P = 0.009), muscle mass [lean mass (MD = 2.73, 95% CI:1.26 to 4.20, P = 0.0003)], muscle strength (MD = 1.90, 95% CI: 0.68 to 3.12, P = 0.002), and physical performance [chair stand test (MD = -2.15, 95% CI: -3.21 to -1.10, P < 0.0001)] in frail older adults compared to control. This meta-analysis and systematic review suggests that dietary supplements interventions positively influence in older people with frailty.

OBJECTIVES: This study investigated whether the serum matrix metalloproteinase-9 level is an independent predictor of recurrence after catheter ablation for persistent atrial fibrillation. METHODS: Fifty-eight consecutive patients with persistent atrial fibrillation were enrolled and underwent catheter ablation. The serum matrix metalloproteinase-9 level was detected before ablation and its relationship with recurrent arrhythmia was analyzed at the end of the follow-up. RESULTS: After a mean follow-up of 12.1±7.2 months, 21 (36.2%) patients had a recurrence of their arrhythmia after catheter ablation. At baseline, the matrix metalloproteinase-9 level was higher in the patients with recurrence than in the non-recurrent group (305.77±88.90 vs 234.41±93.36 ng/ml, respectively, p=0.006). A multivariate analysis showed that the matrix metalloproteinase-9 level was an independent predictor of arrhythmia recurrence, as was a history of atrial fibrillation and the diameter of the left atrium. CONCLUSION: The serum matrix metalloproteinase-9 level is an independent predictor of recurrent arrhythmia after catheter ablation in patients with persistent atrial fibrillation.

Background Berberine acts primarily as an important active ingredient in Coptis chinensis and has been traditionally applied in clinical treatment. Nevertheless, little information has been released about C. chinensis, as far as functional genes and biosynthetic pathway of berberine are concerned. Here, we isolated a novel (S)-canadine synthase gene (designated as CAS-1) from C. chinensis by using RT-PCR and RACE techniques. Results Bioinformatics analysis showed that the cDNA is 1942 bp in length with a complete open reading frame (ORF) of 1476 bp, and the ORF encodes a polypeptide of 491 amino acids with a calculated molecular mass of 55.29 kDa and a pI value of 8.92. Real-time quantitative PCR analysis showed that CcCAS-1 was constitutively expressed in leaf, petiole and rhizome tissues, especially in the leaves of C. chinensis. However, the results of berberine content in different tissues by high-performance liquid chromatography with photodiode array detection (HPLC-DAD) method showed that the leaves and the petiole tissues have similar content of berberine. Conclusions We found that the berberine content in the rhizome was seven times (more or less) than that in the leaves and the petioles. In addition, the full length coding sequence of CcCAS-1 was inserted into pET-32a and was successfully expressed in Escherichia coli, laying a solid foundation for protein purification, activity assay and multi-clonal antibody preparation. Together, our data suggest that CcCAS-1 is a novel heme-thiolate enzyme essential for berberine biosynthesis in C. chinensis.

BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.

Objetivo:Explorar o efeito da eritromicina sobre lesões pulmonares induzidas por hiperóxia.Métodos:Uma prole de ratos Sprague-Dawley (SD) prematuros com um dia de vida foi dividida aleatoriamente em quatro grupos: grupo 1 ar + cloreto de sódio, grupo 2 ar + eritromicina, grupo 3 hiperóxia + cloreto de sódio e grupo 4 hiperóxia + eritromicina. Com um, sete e 14 dias de exposição, foram detectadas Glutationa (GSH) e Interleucina-1 beta (IL-1 beta) pelo ensaio imunossorvente ligado à enzima (ELISA), e o ácido bicinconinico (BCA) foi utilizado para detectar a proteína GSH. O mRNA da γ-glutamil-cisteina-sintetase (γ-GCS) foi detectado por reação em cadeia da polimerase via transcriptase reversa (RT-PCR).Resultados:Comparadas ao grupo 1, as expressões do mRNA da GSH e da γ-GCS no grupo 3 aumentaram significativamente com um e sete dias de exposição (p < 0,05), porém a expressão de mRNA da γ-GCS diminuiu significativamente aos 14 dias; a expressão de IL-1 beta no grupo 3 aumentou significativamente aos 7 dias de exposição (p < 0,05) e diminuiu significativamente aos 14 dias. Comparadas ao grupo 3, as expressões do mRNA da GSH e da γ-GCS no grupo 4 aumentaram significativamente com um, sete e 14 dias de exposição (p< 0,05), porém as expressões de GSH mostraram uma tendência de queda aos 14 dias; a expressão de IL-1 beta no grupo 4 foi reduzida significativamente com um e sete dias de exposição (p < 0,05).Conclusões:As variações de IL-1 beta e GSH mediadas por oxidantes estão envolvidas no desenvolvimento de lesão pulmonar induzida por hiperóxia. A eritromicina poderá regular positivamente a atividade da γ-GCS, aumentando a expressão de GSH, inibindo os níveis de interleucina-1beta mediada por oxidante e aliviando a lesão pulmonar induzida por hiperóxia por meio de um efeito antioxidante.

Objective:To explore the effect of erythromycin on hyperoxia-induced lung injury.Methods:One-day-old preterm offspring Sprague-Dawley (SD) rats were randomly divided into four groups: group 1, air + sodium chloride; group 2, air + erythromycin;group 3, hyperoxia + sodium chloride; and group 4, hyperoxia + erythromycin. At one, seven, and 14 days of exposure, glutathione (GSH) and interleukin-1 beta (IL-1 beta) were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and bicinchoninic acid (BCA) was used to detect GSH protein. γ-glutamine-cysteine synthetase (γ-GCS) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR).Results:Compared with group 1, expressions of GSH and γ-GCS mRNA in group 3 were significantly increased at one and seven days of exposure (p < 0.05), but expression of γ-GCS mRNA was significantly reduced at 14 days; expression of IL-1 beta in group 3 was significantly increased at seven days of exposure (p < 0.05), and was significantly reduced at 14 days. Compared with group 3, expressions of GSH and γ-GCS mRNA in group 4 were significantly increased at one, seven, and 14 days of exposure (p < 0.05), but expressions of GSH showed a downward trend at 14 days; expression of IL-1 beta in group 4 was significantly reduced at one and seven days of exposure (p < 0.05).Conclusions:Changes in oxidant-mediated IL-1 beta and GSH are involved in the development of hyperoxia-induced lung injury. Erythromycin may up-regulate the activity of γ-GCS, increasing the expression of GSH, inhibiting the levels of oxidant-mediated IL-1 beta and alleviating hyperoxia-induced lung injury via an antioxidant effect.

Nossa pesquisa focou-se nas principais características de planejamento e de desempenho de liberação cólon-específica tempo-dependente (TDCS) de comprimidos, que leva em conta a constância relativa observada no tempo de trânsito intestinal das formas de dosagem. A doença inflamatória do intestino (IBD) pode afetar o tempo de trânsito e, geralmente, resulta em fezes aquosas. Comparando ao TDCS e a comprimidos TDCS com matriz-cerosa, investigou-se sistema promissor de liberação cólon-específica tempo-dependente. Em nosso estudo, avaliou-se comprimido revestido com matriz base de supositório. A base de supositório solúvel em água auxilia a expansão do comprimido, facilita a dissolução uniforme do filme e atinge alta pressão osmótica. Associando a expansão do carboximetil amido sódico (CMS-Na) à absorção de umidade do NaCl, o comprimido revestido TDCS originou sistema de liberação direcionado e de erupção. Observou-se correlação muito boa entre a liberação in vitro e a in vivo do fármaco. Este comprimido revestido TDCS representa estratégia promissora para o controle da liberação do fármaco na região gastrintestinal mais baixa.

Our research has focused on the main design features and release performances of time-dependent colon-specific (TDCS) delivery tablets, which relies on the relative constancy that is observed in the small intestinal transit time of dosage forms. But inflammatory bowel disease（IBD）can affect the transit time, and usually results in watery stool. Compared to the TDCS and wax-matrix TDCS tablet, a promising time-dependent colon-specific delivery system was investigated. In our study, a suppository-base-matrix coated tablet was evaluated. Water soluble suppository-base helps the expansion of tablet, facilitates uniform film dissolution and achives high osmotic pressure. Combining the expansion of carboxymethyl starch sodium (CMS-Na) and the moisture absorption of NaCl, the coated TDCS tablet obtained a burst and targeted drug delivery system. A very good correlation between in vitro drug release and in vivo outcome was observed. This TDCS coated tablet provides a promising strategy to control drug release to the desired lower gastrointestinal region.