Search

Background/objectives: Acute kidney injury (AKI) syndrome is distinguished by a quick decline in renal excretory capacity and usually diagnosed by the presence of elevated nitrogen metabolism end products and/or diminished urine output. AKI frequently occurs in hospital patients, and there are no existing specific treatments available to diminish its occurrence or expedite recovery. For an extended period in the food industry, Pediococcus acidilactici has been distinguished by its robust bacteriocin production, effectively inhibiting pathogen growth during fermentation and storage., Methods: In this study, the aim is to assess the effectiveness of P. acidilactici GKA4, dead probiotic GKA4, and postbiotic GKA4 against cisplatin-induced AKI in an animal model. The experimental protocol involves a ten-day oral administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 to mice, with a cisplatin intraperitoneal injection being given on the seventh day to induce AKI., Results: The findings indicated the significant alleviation of the renal histopathological changes and serum biomarkers of GKA4, dead probiotic GKA4, and postbiotic GKA4 in cisplatin-induced nephrotoxicity. GKA4, dead probiotic GKA4, and postbiotic GKA4 elevated the expression levels of HO-1 and decreased the expression levels of Nrf-2 proteins. In addition, the administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 significantly reduced the expression of apoptosis-related proteins (Bax, Bcl-2, and caspase 3), autophagy-related proteins (LC3B, p62, and Beclin1), and endoplasmic reticulum (ER) stress-related proteins (GRP78, PERK, ATF-6, IRE1, CHOP, and Caspase 12) in kidney tissues. Notably, GKA4, dead probiotic GKA4, and postbiotic GKA4 also upregulated the levels of proteins related to organic anion transporters and organic cation transporters., Conclusions: Overall, the potential therapeutic benefits of GKA4, dead probiotic GKA4, and postbiotic GKA4 are significant, particularly after cisplatin treatment. This is achieved by modulating apoptosis, autophagy, ER stress, and transporter proteins to alleviate oxidative stress.

Female Culter alburnus was faster in growth rate than males. In this study, the gynogenetic G2 and the pseudo-male G2' were used as the female and male parents, respectively, to breed a new national variety "All-female No.1" C. alburnus (AFC). Hormone induction, embryonic development, gonadal differentiation, and growth of AFC were studied. The results showed induction with low concentrations of 17α-methyltestosterone in a indoor-net cage culture was not effective. Under the stimulation of 17α-methyltestosterone, some gonads had a tendency to transform into testis, but not completely. There were three types of gonads in 5-month-old and four types of gonads in 12-month-old fishes, however, they all differentiated into ovaries in 15-month-old fishes. Testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction had a good effect resulting in ①a functional pseudo-male with normal testis development that could successfully extrude semen during the breeding period, ②a pseudo-male with normal testis development, but could not extrude semen, and ③the appearance of intersexual glands. The second experiment revealed that with common fish, all-female fish embryo had normal embryonic development. The development time and morphological characteristics of each stage were similar, but the development of the all-female embryo was slightly slower than the common embryos. The gonad differentiation of the all-female embryo were normal and none differentiated into testis, which indicated that all-female could ensure the female sex without affecting the normal gonad differentiation. The correlation between body weight, length, and month-age of all-female and common fish was strong. The all-female had faster growth rate and more uniform growth specification than the common fish. Therefore, the use of testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction could avoid complete degeneration of gonads into ovaries. The all-female embryo had the advantages of normal embryonic development and gonadal differentiation, faster growth, and uniform growth specification., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors reports was provided by Zhejiang Institute of Freshwater Fisheries. The authors reports a relationship with Zhejiang Institute of Freshwater Fisheries that includes: board membership. Li Fei has patent pending to Licensee. The authors declare that there are no competing interests. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Known as COVID-19, it has affected billions of people worldwide, claiming millions of lives and posing a continuing threat to humanity. This is considered one of the most extensive pandemics ever recorded in human history, causing significant losses to both life and economies globally. However, the available evidence is currently insufficient to establish the effectiveness and safety of antiviral drugs or vaccines. The entry of the virus into host cells involves binding to angiotensin-converting enzyme 2 (ACE2), a cell surface receptor, via its spike protein. Meanwhile, transmembrane protease serine 2 (TMPRSS2), a host surface protease, cleaves and activates the virus's S protein, thus promoting viral infection. Plant protease inhibitors play a crucial role in protecting plants against insects and/or microorganisms. The major storage proteins in sweet potato roots include sweet potato trypsin inhibitor (SWTI), which accounts for approximately 60% of the total water-soluble protein and has been found to possess a variety of health-promoting properties, including antioxidant, anti-inflammatory, ACE-inhibitory, and anticancer functions. Our study found that SWTI caused a significant reduction in the expression of the ACE2 and TMPRSS2 proteins, without any adverse effects on cells. Therefore, our findings suggest that the ACE2 and TMPRSS2 axis can be targeted via SWTI to potentially inhibit SARS-CoV-2 infection.

Background: Type-2 diabetes is a chronic progressive metabolic disease resulting in severe vascular complications and mortality risk. Recently, DPP-4 inhibitors had been conceived as a favorable class of agents for the treatment of type 2 diabetes due to the minimal side effects., Methods: Sitagliptin is the first medicine approved for the DPP-4 inhibitor. Its structure involved three fragments: 2,4,5-triflorophenyl fragment pharmacophore, enantiomerically β-amino carbonyl linker, and tetrahydrotriazolopyridine. Herein, we are drawn to the possibility of substituting tetrahydrotriazolopyridine motif present in Sitagliptin with a series of new fused pyrazolopyrimidine bicyclic fragment to investigate potency and safety., Results: Two series of fused 6-(aminomethyl)pyrazolopyrimidine and 6-(hydroxymethyl) pyrazolopyrimidine derivatives containing β-amino ester or amide as linkers were successfully designed for the new DPP-4 inhibitors. Most fused 6-methylpyrazolopyrimidines were evaluated against DPP-4 inhibition and selectivity capacity. Based on research study, β-amino carbonyl fused 6-(hydroxymethyl)pyrazolopyrimidine possesses the significant DPP-4 inhibition (IC 50 ≤ 59.8 nM) and presents similar with Sitagliptin (IC 50 = 28 nM). Particularly, they had satisfactory selectivity over DPP-8 and DPP-9, except for QPP., Conclusion: β-Amino esters and amides fused 6-(hydroxymethyl)pyrazolopyrimidine were developed as the new DPP-4 inhibitors. Those compounds with a methyl group or hydrogen in N -1 position and methyl substituted group in C-3 of pyrazolopyrimidine moiety showed better potent DPP-4 inhibition (IC 50 = 21.4-59.8 nM). Furthermore, they had satisfactory selectivity over DPP-8 and DPP-9 Finally, the docking results revealed that compound 9n was stabilized at DPP-4 active site and would be a potential lead drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To quantify the results of superficial parotidectomy (SP) and partial SP (PSP) for benign parotid tumours using a systematic evaluation method., Methods: A systematic search of English and Chinese databases (PubMed, Web of Science, Cochrane Library, China Knowledge Network, Wanfang and Vipshop) was conducted to include studies comparing the treatment outcomes of SP with PSP., Results: Twenty-three qualified, high-quality studies involving 2844 patients were included in this study. The results of this study showed that compared to the SP surgical approach, the PSP surgical approach reduced the occurrence of temporary facial palsy (OR = 0.33; 95% confidence interval [CI] 0.26-0.41), permanent facial palsy (OR = 0.28; 95% CI 0.16-0.52) and Frey syndrome (OR = 0.36; 95% CI 0.23-0.56) in patients after surgery, and the surgery operative time was reduced by approximately 27.35 min (95% CI - 39.66, - 15.04). However, the effects of PSP versus SP on salivary fistula (OR = 0.70; 95% CI 0.40-1.24), sialocele (OR = 1.48; 95% CI 0.78-2.83), haematoma (OR = 0.34; 95% CI 0.11-1.01) and tumour recurrence rate (OR = 1.41; 95% CI 0.48-4.20) were not statistically significant., Conclusion: Compared with SP, PSP has a lower postoperative complication rate and significantly shorter operative time, suggesting that it could be used as an alternative to SP in the treatment of benign parotid tumours with the right indications., (© 2023. The Author(s).)

We explored the effects of different conditions on the artificial incubation of redclaw crayfish eggs in an effort to improve this process. Samples at the egg and juvenile stages were selected. The samples at different stages were separated from the pleopods, then they were placed in incubator boxes and sterilized with different disinfectant solutions. The density was 300,400 and 500 eggs/incubator box, the vibration frequency was 11,16 and 26 vibrations/min, and the water circulation cycle was 2.1, 4.8 and 7.1 cycles/h. The results showed the eggs disinfected with 3000 ppm formaldehyde for 15 min had stronger antioxidant capacity. The hatching and survival rates of five pairs of appendage stage group were significantly lower than those of other groups. In the egg stage, acid phosphatase (ACP) level of compound eye pigmentation stage group was significantly higher than those of other groups. In the juvenile stage, malondialdehyde (MDA) content of five pairs of appendage stage group was significantly higher than those of other groups. The survival rate of 500 eggs/box group was significantly higher than that of other groups. In the egg stage, alkaline phosphatase (AKP) level of 400 eggs/box group was significantly higher than that of other groups. The survival rate of 11 vibrations/min group was significantly higher than that of other groups. In the egg stage, ACP and AKP levels of 11 vibrations/min group were significantly higher than those of 26 vibrations/min group. In the juvenile stage, superoxide dismutase (SOD), ACP and AKP levels of 11 vibrations/min group was significantly higher than those of 26 vibrations/min group. In the juvenile stage, AKP level of 4.8 cycles/h group was significantly lower than that of other groups. In conclusion, egg development at the stage after seven pairs of appendages, with a density of 400 eggs/box, vibration frequencies set at 11 vibrations/min achieved high hatching rates (93.58 %) and survival rates (75.67 %). Moreover, bronopol or hydrogen peroxide might have a better choice to replace formaldehyde if further exploration was conducted to reduce stimulation of the in vitro-grown egg. These conditions could be used on a large scale to optimize the production of redclaw crayfish., Competing Interests: The authors declare that there are no competing interests., (© 2023 The Authors.)

Coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. This highly contagious pneumonia remains a significant ongoing threat. Uncertainties persist about the virus's effects on human health, underscoring the need for treatments and prevention. Current research highlights angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key targets against SARS-CoV-2. The virus relies on ACE2 to enter cells and TMPRSS2 to activate its spike protein. Inhibiting ACE2 and TMPRSS2 expression can help prevent and treat SARS-CoV-2 infections. Anisomeles indica (L.) Kuntze, a medicinal plant in traditional Chinese medicine, shows various promising pharmacological properties. In this study, ethanolic extracts of A. indica were examined both in vivo (250 and 500 μM) and in vitro (500 μM). Through Western blotting analysis, a significant reduction in the expression levels of ACE2 and TMPRSS2 proteins was observed in HepG2 (human hepatocellular carcinoma) cells and HEK 293T (human embryonic kidney) cell lines without inducing cellular damage. The principal constituents of A. indica , namely, ovatodiolide (5 and 10 μM), anisomlic acid (5 and 10 μM), and apigenin (12.5 and 25 μM), were also found to produce the same effect. Furthermore, immunohistochemical analysis of mouse liver, kidney, and lung tissues demonstrated a decrease in ACE2 and TMPRSS2 protein expression levels. Consequently, this article suggests that A. indica and its constituents have the potential to reduce ACE2 and TMPRSS2 protein expression levels, thus aiding in the prevention of SARS-CoV-2 infections.

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial pneumonia characterized by chronic and progressive fibrosis with an unknown etiology. Previous pharmacological studies have shown that Sanghuangporus sanghuang possesses various beneficial properties including immunomodulatory, hepatoprotective, antitumor, antidiabetic, anti-inflammatory, and neuroprotective effects. This study used a bleomycin (BLM)-induced IPF mouse model to illustrate the possible benefits of SS in ameliorating IPF. BLM was administered on day 1 to establish a pulmonary fibrosis mouse model, and SS was administered through oral gavage for 21 d. Hematoxylin and eosin (H&E) and Masson's trichrome staining results showed that SS significantly reduced tissue damage and decreased fibrosis expression. We observed that SS treatment resulted in a substantial lowering in the level of pro-inflammatory cytokines like TGF-β, TNF-α, IL-1β, and IL-6 as well as MPO. In addition, we observed a notable increase in glutathione (GSH) levels. Western blot analysis of SS showed that it reduces inflammatory factors (TWEAK, iNOS, and COX-2), MAPK (JNK, p-ERK, and p-38), fibrosis-related molecules (TGF-β, SMAD3, fibronectin, collagen, α-SMA, MMP2, and MMP9), apoptosis (p53, p21, and Bax), and autophagy (Beclin-1, LC3A/B-I/II, and p62), and notably increases caspase 3, Bcl-2, and antioxidant (Catalase, GPx3, and SOD-1) levels. SS alleviates IPF by regulating the TLR4/NF-κB/MAPK, Keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 pathways. These results suggest that SS has a pharmacological activity that protects the lungs and has the potential to improve pulmonary fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Prostate cancer (PCa) is the most prevalent men's cancer in America and Western countries. No effective therapies are currently available for PCa aggressiveness, including castration-resistant progression (CRPC). This study aims at evaluation of the prospective efficacy and the molecular mechanism of scandenolone (SCA), a natural isoflavone, in PCa progression. SCA suppressed cell viability and progression and induced apoptosis in PCa cells. SCA inhibited the expression of lipogenesis and cholesterogenesis related key genes. Through inhibition of these metabolic genes, SCA decreased the levels of fatty acids, lipid droplets and cholesterols in PCa cells. Moreover, SCA enhanced the expression of antioxidant factors, including Nrf2, HO-1, catalase and SOD-1, and reduced the ROS levels in PCa cells. Substantially, SCA displayed the potential efficacy on CRPC tumors. This paper offers a new insight into the underlying molecular basis of SCA in PCa cells. By coordinated impairment of the metabolic and signaling vulnerabilities, including lipogenesis, cholesterogenesis, ROS and the AR/PSA axis, SCA could be applied as a novel and promising remedy to cure malignant PCa., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

One of the most popular edible mushrooms in the world, Flammulina velutipes , has been shown to possess pharmacological properties such as anti-inflammatory and antioxidant properties. However, the potential activity of the brown strain of F. velutipes , a hybrid between the white and yellow strains, has not been thoroughly investigated. Numerous studies have been conducted in recent years to determine whether natural products can aid in improving or treating kidney diseases. In this study, we focused on the renoprotective effects of the brown strain of F. velutipes on cisplatin-induced acute kidney injury (AKI) in mice. Mice were pretreated with water extract from the brown strain of F. velutipes (WFV) from day 1 to day 10, with a single-dose intraperitoneal injection of cisplatin on day 7 to induce AKI. Our results demonstrated that WFV administration resulted in a reduction in weight loss and the amelioration of renal function and renal histological changes in mice with cisplatin-induced AKI. WFV improved antioxidative stress and anti-inflammatory capacity by increasing antioxidant enzymes and decreasing inflammatory factors. The expression of related proteins was determined via Western blot analysis, which showed that WFV could improve the expression of apoptosis and autophagy. We used the PI3K inhibitor Wortmannin and found that WFV achieved a protective effect by modulating the PI3K/AKT pathway and the expression of autophagy. Overall, WFV as a natural substance could be used as a new therapeutic agent for AKI.

The current global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of COVID-19 has infected hundreds of millions of people, killed millions, and continues to pose a threat. It has become one of the largest epidemics in human history, causing enormous damage to people's lives and economies in the whole world. However, there are still many uncertainties and continued attention to the impact of SARS-CoV-2 on human health. The entry of SARS-CoV-2 into host cells is facilitated by the binding of the spike protein on the virus surface to the cell surface receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, transmembrane protease serine 2 (TMPRSS2) is a host surface protease that cleaves and proteolytically activates its S protein, which is necessary for viral infection. Thus, SARS-CoV-2 uses the ACE2 receptor for cell entry and initiates the S protein using the protease TMPRSS2. Schizophyllum commune (SC) is one of the most widely distributed fungi, often found on the rotten wood of trees that has been found to have various health benefits, including anticancer, antimicrobial activity, antiparasitic, and immunomodulatory function. In this article, SC significantly diminished the expression ACE2 and TMPRSS2 protein in vitro and in vivo without cell damage. In addition, adenosine from SC was also proven in this experiment to reduce the ACE2 and TMPRSS2 expression. Thus, our findings suggest that SC and adenosine exhibit potential for the repression of SARS-CoV-2 infection via the ACE2 and TMPRSS2 axis.

Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies for the lethal PCa diseases is currently an urgent need. In this study, we endeavored to investigate the therapeutic efficacy of alpinumisoflavone (AIF), a natural product, in PCa. LNCaP (androgen- sensitive) and C4-2 (CRPC) PCa cells were used. An MTT-based method, soft agar colony forming assay, biological progression approaches were applied to determine cell viability, migration, and invasion. A fatty acid quantification kit, a cholesterol detection kit and oil red O staining were conducted to analyze the intracellular levels of lipids and cholesterols. Apoptosis assays were also performed. AIF reduced cell viability, migration, and invasion in PCa cells. The expression of androgen receptor (AR), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was substantially inhibited by AIF treatment in PCa cells. Furthermore, by inhibiting FASN and HMGCR expression, AIF decreased the amounts of intracellular fatty acids, cholesterols, and lipid droplets in PCa cells. Significantly, through coordinated targeting FASN- and HMGCR-regulated biosynthesis and the AR axis, AIF activated the caspase-associated apoptosis in PCa cells. These results collectively demonstrated for the first time the potential of AIF as a novel and attractive remedy and provided an alternative opportunity to cure PCa malignancy.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has led to the most severe global pandemic, which began in Wuhan, China. Angiotensin-converting enzyme 2 (ACE2) combines with the spike protein of SARS-CoV-2, allowing the virus to cross the membrane and enter the cell. SARS-CoV-2 is modified by the transmembrane protease serine 2 (TMPRSS2) to facilitate access to cells. Accordingly, ACE2 and TMPRSS2 are targets of vital importance for the avoidance of SARS-CoV-2 infection. Sanghuangporus sanghuang (SS) is a traditional Chinese medicine that has been demonstrated to have antitumor, antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective and immunomodulatory properties. In this paper, we demonstrated that SS decreased ACE2 and TMPRSS2 expression in cell lines and a mouse model without cytotoxicity or organ damage. Liver and kidney sections were confirmed to have reduced expression of ACE2 and TMPRSS2 by immunohistochemistry (IHC) assessment. Then, hispidin, DBA, PAC, PAD and CA, phenolic compounds of SS, were also tested and verified to reduce the expression of ACE2 and TMPRSS2. In summary, the results indicate that SS and its phenolic compounds have latent capacity for preventing SARS-CoV-2 infection in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Antrodia camphorata is an endemic mushroom in Taiwan. This study was designed to screen anti-inflammatory compounds from the methanolic extract of the mycelium of A. camphorata on nitric oxide (NO) production in RAW 264.7 cells induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA (dsRNA) known to be present in viral infection. A combination of bioactivity-guided isolation with an NMR-based identification led to the isolation of 4-acetylantroquinonol B ( 1 ), along with seven compounds. The structure of new compounds ( 4 and 5 ) was elucidated by spectroscopic experiments, including MS, IR, and NMR analysis. The anti-inflammatory activity of all isolated compounds was assessed at non-cytotoxic concentrations. 4-Acetylantroquinonol B ( 1 ) was the most potent compound against poly I:C-induced NO production in RAW 264.7 cells with an IC 50 value of 0.57 ± 0.06 μM.

Several epidemiological studies have suggested that Epstein-Barr virus (EBV) lytic infection is essential for the development of nasopharyngeal carcinoma (NPC), as the elevation of antibody titers against EBV lytic proteins is a common feature of NPC. Although ZEBRA protein is a key trigger for the initiation of lytic infection, whether its expression affects the prognosis and pathogenesis of NPC remains unclear. In this study, 64 NPC biopsy specimens were analyzed using immunohistochemistry. We found that ZEBRA was significantly associated with a worsening of progression-free survival in NPC (adjusted hazard ratio, 3.58; 95% confidence interval, 1.08-11.87; p = 0.037). Moreover, ZEBRA expression positively correlated with key endocrinological proteins, estrogen receptor α, and aromatase. The transcriptional level of ZEBRA is activated by estrogen in an estrogen receptor α-dependent manner, resulting in an increase in structural gene expression levels and extracellular virus DNA copy number in NPC cell lines, reminiscent of lytic infection. Interestingly, it did not suppress cellular proliferation or increase apoptosis, in contrast with cells treated with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate, indicating that viral production induced by estrogen is not a cell lytic phenomenon. Our results suggest that intratumoral estrogen overproduced by aromatase could induce ZEBRA expression and EBV reactivation, contributing to the progression of NPC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Acute kidney injury (AKI) describes a sudden loss of kidney function and is associated with a high mortality. Pediococcus acidilactici is a potent producer of bacteriocin and inhibits the growth of pathogens during fermentation and food storage; it has been used in the food industry for many years. In this study, the potential of P. acidilactici GKA4 (GKA4) to ameliorate AKI was investigated using a cisplatin-induced animal model. First, mice were given oral GKA4 for ten days and intraperitoneally injected with cisplatin on the seventh day to create an AKI mode. GKA4 attenuated renal histopathological alterations, serum biomarkers, the levels of inflammatory mediators, and lipid oxidation in cisplatin-induced nephrotoxicity. Moreover, GKA4 significantly decreased the expression of inflammation-related proteins and mitogen-activated protein kinase (MAPK) in kidney tissues. Eventually, GKA4 also increased the levels of related antioxidant enzymes and pathways. Consistently, sirtuin 1 (SIRT1) upregulated the level of autophagy-related proteins (LC3B, p62, and Beclin1). Further studies are needed to check our results and advance our knowledge of the mechanism whereby PI3K inhibition (wortmannin) reverses the effect of GKA4 on cisplatin-treated AKI. Taken together, GKA4 provides a therapeutic target with promising clinical potential after cisplatin treatment by reducing oxidative stress and inflammation via the MAPK, AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) axes.

Objective: The aim of this study was to investigate the prognostic value of baseline peripheral blood neutrophils, monocytes, and lymphocytes on locally advanced rectal cancer (LARC) patients., Methods: Clinicopathologic data of 317 LARC patients during July 2010 and October 2016 were retrospectively gathered. X-tile software was used to acquire the optimal cutoff values of neutrophils, monocytes, and lymphocytes. Peripheral blood immune score (PBIS) system was proposed and built based on neutrophils, monocytes, and lymphocytes. The Cox model was used to analyze the associations between clinicopathological characteristics and potential outcomes. C-index was used to assess model performance. A nomogram was constructed to predict prognosis, and a calibration plot was used to verify the accuracy of the nomogram prediction model., Results: Cutoff values of neutrophils, lymphocytes, and monocytes were 4.46 (× 10 9 /L), 1.66 (× 10 9 /L), and 0.39 (× 10 9 /L), respectively. PBIS was related to sex (P < 0.001), tumor length (P = 0.003), and tumor thickness (P = 0.014). Multivariate Cox regression analysis revealed that PBIS (HR = 0.707, 95% CI: 0.549-0.912, P = 0.008) was an independent predictor of DFS. High PBIS (HR = 0.697, 95% CI: 0.492-0.988, P = 0.043) and high lymphocyte count (HR = 0.511, 95%CI: 0.273-0.958, P = 0.036) were favorable factors of OS. Both C-index (0.74, 95% CI: 0.549-0.912) and the calibration plot showed good prediction ability of the nomogram for DFS., Conclusion: PBIS, composed of baseline peripheral blood neutrophils, monocytes, and lymphocytes, is an independent predictor of the prognosis of LARC. Combination of PBIS and ypTNM stage may be a promising marker to guide adjuvant therapy after the operation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Curcumin is proven to have potent anti-inflammatory activity, but its low water solubility and rapid degradation in physiological conditions limit its clinical use, particularly in intravenous drug delivery. In this study, we fabricated rod-shaped, acid-labile nanogels, using high biosafe and biocompatible polymers, for intravenous application in systemic inflammation treatment. The constituent polymers of the nanogels were prepared via the conjugation of vitamin B 6 derivatives, including pyridoxal and pyridoxamine, onto poly(glutamate) with ester bonds. The aldehyde groups of the pyridoxal and amine groups of the pyridoxamine on the polymers enable crosslinking using a Schiff base during the solvent evaporation procedure for the preparation of the rod-shaped nanogels. Our study is the first to introduce this linkage, which is generated from two vitamin B 6 derivatives into a nanogel system. It is also the first to fabricate a rod-shaped nanogel system via simple solvent evaporation. Under acidic conditions, such as those encountered in the endosomes and lysosomes within inflammatory macrophage cells spread in the whole body, imine bonds are cleaved and release payloads. The nanogel polymers were successfully synthesized and characterized, and the formation and disappearance of the Schiff base under neutral and acidic conditions were also confirmed using Fourier transform infrared spectroscopy. Following curcumin encapsulation, the long, rod-shaped nanogels were able to rapidly internalize into macrophage cells in static or adhere to cells under the flows, release their payloads in the acid milieus, and, thus, mitigate curcumin degradation. Consequently, curcumin-loaded, rod-shaped nanogels displayed exceptional anti-inflammatory activity both in vitro and in vivo, by efficiently inhibiting pro-inflammatory mediator secretion. These results demonstrate the feasibility of our acid-labile, rod-shaped nanogels for the treatment of systemic inflammation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in known competing financial interests or personal relationships, having influences in any work in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Castration-resistant prostate cancer (CRPC) is one of the main causes of male cancer mortality. There is currently no effective treatment to cure this deadly prostate cancer (PCa) progression. However, recent research showed that activation of lipogenesis leads to CRPC progression. It provides a rationale to target the highly lipogenic activity as a novel and promising therapy against lethal CRPC., Purposes: The present study aims to evaluate the anticancer efficacy and the molecular mechanism of cell suspension culture extract from Eriobotrya japonica (EJCE) in PCa, including CRPC., Methods: Cell growth, migration and invasion analyses were performed by MTT method, a wound healing assay and the transwell method, respectively. Apoptosis was assessed by a flow cytometry-based Annexin V-FITC/PI assay, caspase enzymatic activity and Western blot analyses. Lipogenesis was determined by a Fatty Acid Quantification Kit and an Oil Red O staining. The in vivo experiment was conducted by a xenograft mouse model., Results: PCa cell growth, migration and invasion were significantly affected by EJCE. EJCE decreased expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN) in PCa cells, two main factors for lipogenesis. By inhibiting SREBP-1/FASN, EJCE reduced the intracellular fatty acid levels and lipid droplet accumulation in PCa. Moreover, EJCE down-regulated the androgen receptor (AR) and prostate-specific antigen (PSA) in PCa cells. Significantly, EJCE exhibited the potential anticancer activity by suppressing the growth and leading to apoptosis of CRPC tumors in a xenograft mouse model., Conclusion: These results reveal a novel therapeutic molecular mechanism of EJCE in PCa. Blockade of SREBP-1/FASN-driven metabolism and AR by EJCE could be employed as a potent opportunity to cure malignant PCa., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Acute kidney injury (AKI) is a sudden reduction in kidney activity and has a high mortality rate. Salvianolic acid C (SAC), one of the main polyphenolic components of Salvia miltiorrhiza , displays significant pharmacologically active effects. An animal model of cisplatin-induced kidney injury was used to study the potential of SAC to improve AKI. First, SAC was administered intraperitoneally in mice for 10 consecutive days, and then cisplatin was administered intraperitoneally on day 7 to establish a nephrotoxicity mouse model. SAC mitigated renal histological changes, blood creatinine (CRE) and blood urea nitrogen (BUN) production and the levels of inflammatory mediators in the cisplatin-induced AKI. Furthermore, malondialdehyde (MDA) levels were reduced and glutathione (GSH) was increased after intraperitoneal injection (i.p.) administration of SAC. In addition, based on Western blot data, SAC reduced the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in mouse renal tissues. Finally, SAC diminished the level of TLR-4 expression and enhanced the production of several antioxidative enzymes (superoxidase dismutase (SOD1), glutathione peroxidase (GPx3), catalase, nuclear-factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1)), Sirtuin 1 (Sirt1), p-AMP-activated protein kinase (AMPK) and p-Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKK). In addition, Sirt1 inhibition (EX 527) inverted the effect of SAC against cisplatin-induced nephrotoxicity. Collectively, SAC provides a therapeutic target with promising clinical potential after cisplatin treatment by attenuating oxidative stress and inflammation.

Objective: To investigate the clinical effects of ulnar artery perforator chain flaps in repairing wounds on distal forearm or wrist with vascular anastomosis. Methods: The retrospective observational study method was used. From March 2015 to July 2019, a total of 11 serious trauma patients on distal forearm or wrist with vascular injury were admitted to the Second Hospital of Tangshan, including 8 male patients and 3 female patients, aged from 25 to 62 years, with an average age of 45 years. Vascular anastomosis and tendon repair were performed in all patients, and fracture reduction and fixation were conducted in 9 patients, of which 8 patients underwent external fixation of radius. The residual wounds were located in palmar distal forearm in 5 patients, palmar wrist in 4 patients, dorsal distal forearm in 1 patient, and dorsal wrist in 1 patient, with wound sizes ranged from 4.5 cm×3.0 cm to 10.0 cm×6.0 cm after the last debridement. The wounds were repaired with ulnar artery perforator chain flaps, with the flap sizes ranged from 5.2 cm×3.5 cm to 11.0 cm×7.0 cm. The wound in flap donor site of 1 patient was sutured directly, the wounds in flap donor sites of the other 10 patients were repaired with free skin grafts from ipsilateral thigh after being sutured partially, and the sizes of free skin grafts ranged from 4.0 cm×2.0 cm to 8.5 cm×5.0 cm. The survivals of flaps, skin grafts, and injured limbs after operation were observed. The appearances of the flaps and donor sites of flaps were observed during follow-up. At the final follow-up, the static two-point discrimination distances of the flaps were measured, and the satisfaction degrees of patients for the appearances of injured limbs were evaluated based on Michigan Hand Function Questionnaire. Results: All flaps, skin grafts, and injured limbs survived after operation, without wound infection and blister formation. All patients were followed up for 8 to 26 months, the appearances of the flaps were good and not bloated, with similar color, texture, and thickness to the surrounding skin. The donor sites of flaps repaired with skin grafts were smooth, with circle scar at the edges. At the final follow-up, the static two-point discrimination distances of the flaps was 10-15 mm; 7 patients were strongly satisfied with the appearances of the injured limbs, and the remaining 4 patients were satisfied with the appearances of flaps. Conclusions: The ulnar artery perforator chain flap has constant vascular anatomy and reliable blood supply, with simple operation, which provides a good treatment method for repairing wounds on distal forearm or wrist with vascular anastomosis. It is especially suitable for the patients with radius fracture fixed by external fixator.

"Iron prawn" is a condition of severe growth retardation that fishers call. The giant river prawn (Macrobrachium rosenbergii) is a commercially important species contains high protein content and functional nutrients. However, no proteomic information is available for this species. We performed the shotgun 2DLC-MS/MS proteomic analysis of the total protein from "iron prawn". Total 19,758 peptides corresponding to 2613 high-confidence proteins were identified. These proteins range in size from 40 to 70 kDa. KEGG analysis revealed that the largest group consisting total 102 KEGG pathway proteins comparing the "iron prawn" with the normal prawn. Additionally, 7, 11, 1, 6, and 5 commercially important enzymes were found in the eyestalk, liver, muscle, ovary, and testis, respectively. The functions of these differently expressed enzymes include immune system action against pathogens, muscle contraction, digestive system metabolism, cell differentiation, migration, and apoptosis in the severe growth retardation of "iron prawn". Our work provides insight into the understanding of the formation mechanism of "iron prawn"., (Copyright © 2021. Published by Elsevier B.V.)

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca 2+ /calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

In this study we prepared six types of carbon nanodots (CNDs) from natural plant materials - through carbonization of two species of bamboo (Bamboo-I, Bamboo-II) and one type of wood (Wood), and through hydrothermal processing of the stem and root of the herb Mahonia oiwakensis Hayata (MO) and of the agricultural waste of two species of pineapple root (PA, PB). The resulting CNDs were spherical with dimensions on the nanoscale (3-7 nm); furthermore, CND-Bamboo I, CND-Wood, CND-Bamboo II, CND-MO, CND-PA, and CND-PB displayed fluorescence quantum yields of 9.63, 12.34, 0.90, 10.86, 0.35, and 0.71%, respectively. X-ray diffraction revealed that the carbon nanostructures possessed somewhat ordered and disordered lattices, as evidenced by broad signals at values of 2 θ between 20 and 30°. CND-Bamboo I, CND-Wood, and CND-Bamboo II were obtained in yields of 2-3%; CND-MO, CND-PA, and CND-PB were obtained in yields of 17.64, 9.36, and 22.47%, respectively. Cytotoxicity assays for mouse macrophage RAW264.7 cells treated with the six types of CNDs and a commercial sample of Ag nanoparticles (NPs) revealed that each of our CNDs provided a cell viability of 90% at 2000 μg mL -1 , whereas it was only 20% after treatment with the Ag NPs at 62.5 μg mL -1 . The six types of CNDs also displayed low cytotoxicity toward human keratinocyte HacaT cells, human MCF-7 breast cancer cells, and HT-29 colon adenocarcinoma cells when treated at 500 μg mL -1 . Moreover, confocal microscopic cell imaging revealed that the fluorescent CND-Bamboo I particles were located on the MCF-7 cell membrane and inside the cells after treatment for 6 and 24 h, respectively. We have thoroughly investigated the photoluminescence properties and carbon nanostructures of these highly dispersed CNDs. Because of the facile green synthesis of these six types of CNDs and their sourcing from abundant natural plants, herbs, and agriculture waste, these materials provide a cost-effective method, with low cytotoxicity and stable fluorescence, for biolabeling and for developing cell nanocarriers., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Purpose: Cervical cancer (CC) is one of the most general gynecological malignancies and is associated with high morbidity and mortality. We aimed to select candidate genes related to the diagnosis and prognosis of CC., Methods: The mRNA expression profile datasets were downloaded. We also downloaded RNA-sequencing gene expression data and related clinical materials from TCGA, which included 307 CC samples and 3 normal samples. Differentially expressed genes (DEGs) were obtained by R software. GO function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed in the DAVID dataset. Using machine learning, the optimal diagnostic mRNA biomarkers for CC were identified. We used qRT-PCR and Human Protein Atlas (HPA) database to exhibit the differences in gene and protein levels of candidate genes., Results: A total of 313 DEGs were screened from the microarray expression profile datasets. DNA methyltransferase 1 (DNMT1), Chromatin Assembly Factor 1, subunit B (CHAF1B), Chromatin Assembly Factor 1, subunit A (CHAF1A), MCM2, CDKN2A were identified as optimal diagnostic mRNA biomarkers for CC. Additionally, the GEPIA database showed that the DNMT1, CHAF1B, CHAF1A, MCM2 and CDKN2A were associated with the poor survival of CC patients. HPA database and qRT-PCR confirmed that these genes were highly expressed in CC tissues., Conclusion: The present study identified five DEmRNAs, including DNMT1, CHAF1B, CHAF1A, MCM2 and Kinetochore-related protein 1 (KNTC1), as potential diagnostic and prognostic biomarkers of CC., (© 2021 The Author(s).)

The near-surface part of the crust, also called the skin of the earth, is the arena of human activity of which the stiffness is of great concern to engineers in infrastructure construction. The stiffness reduction of near-surface geomaterials also plays a vital role in geohazards triggering. However, the physical mechanism behind the material softening is still not fully understood. Here, we report a coseismic shear-wave velocity reduction in the near surface by up to a few tens of percent during the strongest shaking from the 11 March 2011 Tohoku-Oki Earthquake and a subsequent two-stage healing process including a rapid recovery within a few minutes and a slow recovery over many years. We also present a theoretical contact model between mineral grains in geomaterials containing multiple metastable contacts at small separations due to the oscillatory hydration interaction, which can explain the emergence of different stages in the healing process.

This study applied RNA-seq technology to discover reproduction-related genes and pathways in female topmouth culter brain (including pituitary) and ovarian tissues. In functional analysis, 2479 and 2605 unigenes in the brain and ovary tissue were assigned to the "reproductive process" subcategory in addition to the 2660 and 2845 unigenes assigned to the "reproduction" subcategory. Twenty-three complete cDNA sequences were identified through the different gene expression (DGE) approach from five reproduction-related pathways (MAPK signaling pathway, neuroactive ligand-receptor interaction pathway, gonadotropin-releasing hormone signaling pathway, oocyte meiosis pathway, and steroid biosynthesis pathway). The expression levels of 16 candidate genes using qPCR in this study were in accordance with the results of transcriptome analysis. In addition, the expression levels of the FSH, 3β-HSD, PGR, and NPYR genes in malformed gynogenetic ovaries were considerably low, which was consistent with the progress of oocytogenesis in the ovaries of topmouth culter. The high expression of these four genes in the ovaries of normal topmouth culter suggested they might involve in the preparation for the shift of oogenesis to ovulation. Hence, our work identified a set of annotated gene products that are candidate factors affecting reproduction in the topmouth culter H-P-G axis. These results could be essential for further research in functional genomics and genetic editing for topmouth culter reproduction.

A new method was developed for synthesis of 1,2,4-triazole-3-carboxylates 5a-p and 6 from nitrilimines 3a-p through amination and heterocyclization two-steps reactions. All of 1,2,4-triazole-3-carboxylates 5 and 6 were characterized by spectroscopy technique. Based on the SAR study of anti-inflammation activity, most of these compounds showed potential anti-inflammatory activity on NO inhibition in LPS-induced RAW 264.7 cells (IC 50  < 7.0 µM) compared with Celecoxib and Indomethacin. Several potential compounds 5b-h, 5j, 5l, 5n, and 5o were subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. Compound 5d showed extraordinary COX-2 inhibition (IC 50  = 17.9 nM) and the best selectivity (COX-1/COX-2 = 1080). Furthermore, 5 mg/kg compound 5d exhibited better in vivo anti-inflammation and gastric protection results compared to 10 mg/kg Indomethacin. Docking experiments of 5d into COX-2 binding pocket have been evaluated. Following the bioactivities experimental data, the potential drug candidate 5d, significantly exhibited better anti-inflammatory effect than Indomethacin., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The anti-inflammatory effect of hispolon has identified it as one of the most important compounds from Sanghuangporus sanghuang . The research objectives were to study this compound using an animal model by lipopolysaccharide (LPS)-induced acute lung injury. Hispolon treatment reduced the production of the pro-inflammatory mediator NO, TNF-α, IL-1β, and IL-6 induced by LPS challenge in the lung tissues, as well as decreasing their histological alterations and protein content. Total cell number was also reduced in the bronchoalveolar lavage fluid (BALF). Moreover, hispolon inhibited iNOS, COX-2 and IκB-α and phosphorylated IKK and MAPK, while increasing catalase, SOD, GPx, TLR4, AKT, HO-1, Nrf-2, Keap1 and PPARγ expression, after LPS challenge. It also regulated apoptosis, ER stress and the autophagy signal transduction pathway. The results of this study show that hispolon regulates LPS-induced ER stress (increasing CHOP, PERK, IRE1, ATF6 and GRP78 protein expression), apoptosis (decreasing caspase-3 and Bax and increasing Bcl-2 expression) and autophagy (reducing LC3 I/II and Beclin-1 expression). This in vivo experimental study suggests that hispolon suppresses the LPS-induced activation of inflammatory pathways, oxidative injury, ER stress, apoptosis and autophagy and has the potential to be used therapeutically in major anterior segment lung diseases., Competing Interests: All authors have no conflicts of interests exists.

Background: Mesenchymal stem cells (MSCs) are under consideration for myocardial ischemia-reperfusion (I/R) injury therapy, but their mechanism remains to be evaluated. In this article, we aimed to study the effects of the miR-29a/follistatin-like 1 axis in bone marrow-derived mesenchymal stem cells on modulating myocyte apoptosis after hypoxia-reoxygenation (H/R) injury., Methods: An in vitro myocardial ischemia-reperfusion injury model of H9c2 cells was developed by hypoxia-reoxygenation injury. The mRNA levels of follistatin-like 1, Bcl-2, Bax, and miR-29a and the protein levels of Bcl-2, Bax, cleaved caspase-3, and components of the JAK2/STAT3 pathway were detected by qRT-PCR and western blotting, respectively. Secretion of follistatin-like 1 was evaluated by enzyme-linked immunosorbent assay. Cell apoptosis was evaluated by flow cytometry. The interaction between miR-29a and follistatin-like 1 was evaluated by dual luciferase reporter assay., Results: MiR-29a suppressed the expression and secretion of follistatin-like 1 in bone marrow-derived mesenchymal stem cells. Overexpression of follistatin-like 1 in bone marrow-derived mesenchymal stem cells decreased apoptosis of myocytes induced by hypoxia-reoxygenation. Cell apoptosis in myocytes was promoted by conditioned medium from bone marrow-derived mesenchymal stem cells with ectopic miR-29a expression. Conditioned medium of miR-29a-overexpressing bone marrow-derived mesenchymal stem cells inhibited the JAK2/STAT3 pathway in myocytes to promote apoptosis of myocytes., Conclusions: MiR-29a in bone marrow-derived mesenchymal stem cells inhibits follistatin-like 1 secretion and promotes myocyte apoptosis by suppressing the JAK2/STAT3 pathway in hypoxia-reoxygenation injury., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods : LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted., Results: DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model., Conclusions: These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa .

Reports a case of diabetic foot patient with right toe pain, ulceration for 4 years and aggravation for 1 month. After rigorous medical treatment and related examinations, transeversal bone transfer of tibia was proposed. However, the skin condition on the inner side of the lower leg was not good before the operation, so the transversal bone removal of the fibula was performed. Two segments of the lateral fibula were osteotomized with miniature osteotomies. The two osteotomy lines were about 10 cm apart. The distal osteotomy line is about 10 cm from the tip of the lateral malleolus. On the 8th day after the surgery, the bone was moved every 6 hours and was extended inwards by 1 mm every day. After 14 days, the bone was moved back for another 14 days. Skin temperature from preoperative to postoperative, ankle brachial index, CT angiography, CT value, visual analogue scale (VAS) of pain and wound healing were evaluated by comparison. The wound was completely healed 28 days after the operation.

In this study, for the first time, we precisely assembled the poly-γ-benzyl-l-glutamate and an amphiphilic copolymer d-α-tocopherol polyethylene glycol succinate into a mixed micellar system for the embedment of the anticancer drug doxorubicin. Importantly, the intracellular drug-releasing behaviors could be controlled by changing the secondary structures of poly-γ-benzyl-l-glutamate via the precise regulation of the buffer's pH value. Under neutral conditions, the micellar architectures were stabilized by both α-helix secondary structures and the microcrystalline structures. Under acidic conditions (pH 4.0), the interior structures transformed into a coil state with a disordered alignment, inducing the release of the loaded drug. A remarkable cytotoxicity of the Dox-loaded mixed micelles was exhibited toward human lung cancer cells in vitro. The internalizing capability into the cancer cells, as well as the intracellular drug-releasing behaviors, were also identified and observed. The secondary structures containing Dox-loaded mixed micelles had an outstanding antitumor efficacy in human lung cancer A549 cells-bearing nude mice, while little toxicities occurred or interfered with the hepatic or renal functions after the treatments. Thus, these pH-tunable α-helix-containing mixed micelles are innovative and promising for controlled intracellular anticancer drug delivery.

Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF- α , IL-1 β , and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF- κ B) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF- κ B activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds-adenosine and N6-(2-hydroxyethyl) adenosine (HEA)-inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro . Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation., Competing Interests: All authors have no conflicts of interests., (Copyright © 2020 Jeng-Shyan Deng et al.)

12- epi-Lycopodine (1), a Lycopodium alkaloid, along with lycopodine (2) and huperzine A (3), were discovered in the mycelium of Paraboeremia sp. Lsl3KI076, a UV-irradiated strain of Paraboeremia sp. Lsl3, an endophytic fungus from Lycopodium serratum Thunb. var. longipetiolatum Spring. Additionally, a trace of 1 was isolated from Phlegmariurus nummulariifolius (Blume) Ching, and the structure was elucidated on the basis of spectroscopic data. This is the first report proving that a new naturally occurring Lycopodium alkaloid can be obtained from an endophytic fungus.

For patients with nonvalvular atrial fibrillation (NVAF) receiving warfarin therapy, the target international normalized ratio range of 2.0 to 3.0 is recommended by Western countries. However, this treatment carries a higher risk of bleeding which suggests more researches on whether low-intensity warfarin therapy (range <2.0 to 3.0) is suitable for East Asian patients. Three databases were searched from inception to April 21, 2016. Studies that reported thromboembolic and hemorrhagic events in low- and standard-intensity warfarin groups were included. Finally, seven studies were included in the analysis. There was a significantly decreased risk of hemorrhagic events (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.43 to 0.82, p = 0.002) with no statistically increased risk of thromboembolic events (OR 1.14, 95% CI 0.80 to 1.62, p = 0.47) in the 1.5 to 2.0 group compared with that of the 2.0 to 3.0 group. Meanwhile, there was no significant difference of cardiovascular mortality (OR 1.58, 95% CI 0.89 to 2.83, p = 0.12) between the 2 groups. Further analysis showed there was no significance in thromboembolic events (OR 1.15, 95% CI 0.83 to 1.60, p = 0.40), major bleeding events (OR 0.74, 95% CI 0.50 to 1.09, p = 0.13), and cardiovascular mortality (OR 1.45, 95% CI 0.79 to 2.65, p = 0.23) between 1.5 to 2.5 and 2.0 to 3.0 groups. Although no significant difference was found in hemorrhagic events (OR 0.76, 95% CI 0.57 to 1.01, p = 0.06), there was a decreased trend in it. In conclusion, low-intensity warfarin therapy can achieve reduced hemorrhage without increasing thromboembolism for East Asian patients with NVAF receiving warfarin therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To establish the induced pluripotent stem cells (iPSCs) from patients with arrhythmogenic right ventricular cardiomyopathy (ARVC)., Methods: The fibroblasts were isolated from ARVC patient and DNA mutation sites were confirmed. We reprogrammed the patient fibroblasts to pluripotency by sendaiviral transduction with defined pluripotency factors. Then, we evaluated the pluripotency of ARVC-iPSCs by performing the immunofluorescence analysis, real-time PCR and 3 germ layer formation assay. We also induced the ARVC-iPSCs into cardiac specific differentiation by regulating Wnt signaling pathway., Results: Apart from alkaline phosphatase positive staining, iPSCs derived from ARVC patients expressed pluripotent related genes and embryonic stem cell marker OCT4, SSEA4 and TRA-1-81. Embryonic body formation in vitro and teratoma test in vivo demonstrated that ARVC-iPSCs could differentiate into all three germ layers. After in vitro cardiac differentiation, ARVC-iPSC could be successfully induced to spontaneously beating mass with cTNT staining positive., Conclusions: Induced pluripotent stem cell was successfully established by integration free sendai virus from dermal fibroblast of patients with ARVC. It would provide the valuable experimental model to study the molecular mechanism of ARVC.

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1β, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation., Competing Interests: The authors declare no conflicts of interest.

Three new Lycopodium alkaloids, serralongamines B-D (1-3), have been isolated from the club moss Lycopodium serratum var. longipetiolatum, and the structures were elucidated on the basis of spectroscopic data and chemical transformation. 1 and 3 significantly exhibited the inhibitory activity against foam cell formation in human macrophages, one of characteristic features of early atherosclerotic lesions., (Copyright © 2016. Published by Elsevier Ltd.)

Purpose: Clinically, some patients with stage pT2N0M0 esophageal squamous cell carcinoma (ESCC) might have poor survival outcomes after Ivor-Lewis esophagectomy. We explored whether adjuvant radiotherapy could improve the prognosis for the patients with high risk of poor clinical outcomes., Methods: We screened 326 pT2N0M0 ESCC patients who had complete resection with Ivor-Lewis esophagectomy. The expression profile of Ku80 was examined by immunohistochemistry and validated by Western blotting. Patients with high expression of Ku80 were divided randomly into the adjuvant radiotherapy group and control group. Patients with low expression of Ku80 were enrolled into the negative group. The overall survival (OS) and disease-free survival (DFS) was determined by Kaplan-Meier and log-rank analysis., Results: According to receiver operating characteristics curve analysis of Ku80 expression, 124 patients were enrolled into the negative group, 106 patients into the radiotherapy group, and 106 patients into the control group. Log-rank analysis showed that patients in the control group had worse OS and DFS than those in the negative group (P < 0.001, P < 0.001). There is no difference in OS and DFS of patients between radiotherapy group and negative group (P = 0.166, P = 0.648). Patients in the radiotherapy group had significantly better OS and DFS than those in the control group (P = 0.007, P < 0.001). Multivariate analysis further suggested that adjuvant radiotherapy was an independent prognostic indicator for patients with Ku80 overexpression., Conclusions: In stage pT2N0M0 ESCC, Ku80 can be exploited as a predictor to identify patients with high risk of poor prognosis. Adjuvant radiotherapy could significantly improve survival for the patients with Ku80 overexpression.

Objectives: To analyse the microbia composition of 10 healthy dental implants and 10 chronic periodontitis patients., Methods: Subgingival plaque and peri-implant biofilm were sampled at the first molar site before and after implant restoration. The analysis was conducted by 454-prosequencing of bacterial V1 to V3 regions of 16S rDNA., Results: Chronic periodontitis subjects showed greater bacterial diversity compared with implant subjects. The relative abundance of sixteen genera and twelve species differed significantly between implant and chronic periodontitis subjects. The genera Catonella, Desulfovibrio, Mogibacterium, Peptostreptococcus and Propionibacterium were present in higher abundance in chronic periodontitis subjects, while implant subjects had higher proportions of Brevundimonas and Pseudomonas species., Conclusions: Our results demonstrate that implant restoration changes the oral microbiota. The analysis suggests that periodontal bacteria can remain for a prolonged period of time at non-dental sites, from where they can colonise the peri-implant.

Saliva diagnostics utilizing nanotechnology and molecular technologies to detect oral squamous cell carcinoma (OSCC) has become an attractive field of study. However, no specific methods have been established. To refine the diagnostic power of saliva peptide fingerprints for the early detection of OSCC, we screened the expression spectrum of salivary peptides in 40 T1 stage OSCC patients (and healthy controls) using MALDI-TOF-MS combined with magnetic beads. Fifty proteins showed significantly different expression levels in the OSCC samples (P<0.05). Potential biomarkers were also predicted. The novel diagnostic proteomic model with m/z peaks of 1285.6 Da and 1432.2 Da are of certain value for early diagnosis of OSCC., (© 2015 The Authors.)

Objectives: Investigate the role of the epithelial-mesenchymal interaction of keratocystic odontogenic tumor (KCOT) in influencing osteoclastogenesis., Materials and Methods: Fibroblasts isolated from KCOT fibrous capsule and normal gingival mucosa were, respectively, co-cultured with human immortalized oral epithelial cells (HIOECs), and the supernatant was collected to make conditioned medium, in which the osteoclastogenesis of osteoclast precursor cell line Raw 264.7 was observed. Genes related to bone resorption (RANKL, OPG, COX-2, and M-CSF) were analyzed by real-time PCR. Antibodies against human sRANKL and inhibitor of COX-2: NS398 were added to conditioned medium to investigate the inhibitory effect on osteoclastogenesis., Results: Compared with co-cultured gingival fibroblasts and HIOECs (GE-CM), the conditioned medium from co-cultured KCOT fibroblasts and HIOECs (KE-CM) induced more osteoclast-like cell formation and increased NFATC1 mRNA in Raw264.7 cells (P < 0.05). Co-cultured KCOT fibroblasts (KF) and HIOECs, respectively, expressed more COX-2 mRNA than the co-cultured gingival fibroblasts (GF) and HIOECs (P < 0.05). While the ratio of RANKL/OPG in HIOECs co-cultured with KF was also significantly higher than that co-cultured with GF (P < 0.05). The anti-human sRANKL antibody in KE-CM inhibited osteoclastogenesis of Raw264.7 cells; however, NS398 displayed little inhibition., Conclusion: An interesting phenomenon of osteoclastogenic effect of KE-CM in vitro was investigated, which suggested an indispensable role of epithelial-mesenchymal interaction of KCOT in its bone destruction. It could be at least partly attributed to the up-regulated ratio of RANKL/OPG in epithelium induced by KCOT fibroblasts, the aggressiveness of tumor as result of epithelial-mesenchymal interaction deserves exploration further., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To investigate the relationship between KCNN3 SNP (single-nucleotide polymorphism) rs13376333 and risk of atrial fibrillation (AF) and to provide evidence for prevention and treatment for AF.The PubMed, Embase, OVID, Cochrane library, CNKI, and Wan Fang databases were searched to identify studies on the relationship between KCNN3 SNP rs13376333 polymorphism and atrial fibrillation. Two authors performed independent article reviews and study quality assessment using the Newcastle-Ottawa Scale (NOS) checklist.Seven studies involving 24,339 individuals were included in the meta-analysis. The overall combined OR of rs13376333 polymorphism was observed for both lone AF (OR: 1.58 [95%CI: 1.37 to 1.82]; P < 0.001; I(2) = 47.0%) and total AF (OR: 1.33 [95%CI: 1.14 to 1.54]; P < 0.001; I(2) = 0). Further, when stratified by ethnicity, control sources, sample sizes, and genotyping method, similar results were observed in both subgroups. Sensitivity analysis revealed that the source of control was the source of the heterogeneity for lone AF. Omission of any single study had little effect on the combined risk estimate. No evidence of publication bias was found.This meta-analysis suggests that KCNN3 SNP rs13376333 polymorphism significantly increases the risk of lone AF and total AF, which suggests the rs13376333 polymorphism of the KCNN3 gene may play an important role in the pathogenesis of AF.

The topmouth culter (Culter alburnus) is an economically important freshwater fish, which is widely distributed throughout large rivers, reservoirs, and lake areas of China. We report here the isolation and characterization of 32 new polymorphic microsatellite loci isolated from genomic DNA in this species enriched by (CA)12 and (GA)12 probes. The variability of these microsatellites was tested on 30 individuals cultured. The average allele number was 6.6 per locus, ranging from 3 to 12. The observed heterozygosity was from 0.4667 to 0.9000, and the expected heterozygosity was from 0.6163 to 0.9085. After using Bonferroni's correction for multiple tests, there was no evidence of linkage disequilibrium between pairs of loci, but deviations from Hardy-Weinberg equilibrium were found in 3 loci. These microsatellites can be used to study QTL of economic importance, population genetic diversity and the construction of genetic maps for C. alburnus in the future.