A Review on Extracts, Chemical Composition and Product Development of Walnut Diaphragma Juglandis Fructus.

Walnuts are one of the world's most important nut species and are popular for their high nutritional value, but the processing of walnuts produces numerous by-products. Among them, Diaphragma Juglandis Fructus has attracted the attention of researchers due to its complex chemical composition and diverse bioactivities. However, comprehensive reviews of extract activity and mechanistic studies, chemical composition functionality, and product types are scarce. Therefore, the aim of this review is to analyze the extracts, chemical composition, and product development of Diaphragma Juglandis Fructus. Conclusions: For extracts, the biological activities of aqueous and ethanol extracts have been studied more extensively than those of methanol extracts, but almost all of the studies have been based on crude extracts, with fewer explorations of their mechanisms. For chemical composition, the bioactivities of polyphenols and polysaccharides were more intensively studied, while other chemical constituents were at the stage of content determination. For product development, walnuts are mainly used in food and medicine, but the product range is limited. In the future, research on the bioactivity and related mechanisms of Diaphragma Juglandis Fructus can be further expanded to improve its value as a potential natural plant resource applied in multiple industries.

Molecular Docking Revealed the Potential Anti-Oxidative Stress Mechanism of the Walnut Polypeptide on HT22 Cells.

The preparation of novel antioxidant peptides from food raw materials is one of the research focuses, but there are fewer studies on the preparation of antioxidant peptides from walnut meal, a by-product of processing walnuts. This study analyzed the antioxidant properties and protective effects of walnut protein hydrolyzed by alkaline protease and trypsin on the oxidative stress of HT22 cells. The peptides were identified by UPLC-MS/MS, and the anti-oxidative peptides were screened based on virtual computer tools. The potential anti-oxidative stress mechanism of the walnut polypeptide on HT22 cells was explored by molecular docking. The results revealed that walnut protein hydrolysates (WPH) with molecular weights of less than 1 kDa had good antioxidant properties and inhibited oxidative damage of HT22 cells by regulating the levels of reactive oxygen species (ROS) and antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Six of the ninety identified new peptides showed good solubility, non-toxicity, and bioactivity. The molecular docking results showed that the six peptides could dock with Keap1 successfully, and EYWNR and FQLPR (single-letter forms of peptide writing) could interact with the binding site of Nrf2 in the Keap1-Kelch structural domain through hydrogen bonds with strong binding forces. The results of this study provided important information on the antioxidant molecular mechanism of the walnut polypeptide and provided a basis for further development of walnut antioxidant polypeptide products.

Anti-inflammatory and gut microbiota regulatory effects of walnut protein derived peptide LPF in vivo.

Walnut peptides have been reported to exhibit diverse activities. In this study, we investigated the protective and recovery effects of the walnut derived peptide leucine-proline-phenylalanine (LPF) on dextran sulfate sodium (DSS)-induced colitis in mice. The peptide LPF mitigated the severity of symptoms during the development phase of colitis, as evidenced by changes in body weight, disease activity index score, and serum inflammatory cytokine levels. Moreover, the treatment groups showed beneficial effects, including increased colon length, reduced colonic cell apoptosis, decreased production of inflammatory factors, and expansion of splenic regulatory T cells during the recovery period. Additionally, 16S rDNA sequencing results indicated that 100 mg/kg LPF (M group) reversed the dysbiosis of gut microbiota in colitis mice. This included partial recovery of diversity of microbiota, increase in relative abundance of the family Lachnospiraceae and Ruminococcaceae during the development phase of colitis. Additionally, the composition of gut microbiota in the M group was constantly improved during the recovery period of colitis, showing increased relative abundance of beneficial genera and decreased abundance of potentially harmful genera compared with that in the DSS group. In summary, the peptide LPF could contribute to remission of colitis symptoms and restoration through reduction in cell apoptosis, anti-inflammatory effects, and regulation of gut microbiota.

Osteopontin Promotes Trophoblast Invasion in the Smooth Muscle Cell-Endothelial Co-Culture At Least Via Targeting Integrin αvß3.

Preeclampsia is a pregnancy disorder, whereas the underlying mechanisms and etiological factors of this complication remain elusive. Studies have reported that decreased invasiveness of trophoblast cells, immunity disorder in the maternal-fetal interface, and oxidative stress may contribute to the development of preeclampsia. In the present study, we firstly co-cultured the smooth muscle cells (SMCs) and endothelial cells (ECs) to mimic the decidua and myometrium interface and examined the effects of osteopontin (OPN) on the invasive potential of trophoblasts in the SMC-EC co-culturing system. Our results showed that HTR-8/SVneo cells after hypoxia treatment showed enhanced invasive potential in the SMC-EC co-culturing system. OPN levels in the culture media from hypoxia-treated HTR-8/SVneo cells were significantly increased. More importantly, OPN treatment upregulated integrin, beta 3 and integrin, beta 5 expression in HTR-8/SVneo cells, and promoted HTR-8/SVneo cell invasion in the transwell invasion assay and SMC-EC co-culturing system. Mechanistically, treatment with integrin αvß3 inhibitor significantly attenuated the enhanced invasive potential of HTR-8/SVneo cells treated with OPN in the SMC-EC co-culturing system. In conclusion, our study for the first time established the SMC-EC co-culturing system to examine the invasive potential of trophoblasts. Our results indicated that OPN promoted the invasive capacity of trophoblasts via at least targeting αvß3 in the EC-SMC co-culturing system. Future studies were required to further validate the EC-SMC co-culturing system and to determine the molecular mechanisms of OPN-mediated trophoblast invasion.

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study.

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%-2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2-14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1-14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5-9) versus 11 d (IQR: 8-13), P < 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.

Ginsenoside Rg1 Ameliorates Behavioral Abnormalities and Modulates the Hippocampal Proteomic Change in Triple Transgenic Mice of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, so far, there are no effective measures to prevent and cure this deadly condition. Ginsenoside Rg1 (Rg1) was shown to improve behavioral abnormalities in AD; however, the potential mechanisms remain unclear. In this study, we pretreated 7-month-old 3xTg-AD mice for 6 weeks with Rg1 and evaluated the effects of Rg1 on the behaviors and the protein expression of hippocampal tissues. The behavioral tests showed that Rg1 could improve the memory impairment and ameliorate the depression-like behaviors of 3xTg-AD mice. Proteomic results revealed a total of 28 differentially expressed hippocampal proteins between Rg1-treated and nontreated 3xTg-AD mice. Among these proteins, complexin-2 (CPLX2), synapsin-2 (SYN2), and synaptosomal-associated protein 25 (SNP25) were significantly downregulated in the hippocampus of 3xTg-AD mice compared with the WT mice, and the treatment of Rg1 modulated the expression of CPLX2 and SNP25 in the hippocampus of 3xTg-AD mice. The expression of CPLX2, SYN2, and SNP25 was further validated by Western blot analysis. Taken together, we concluded that Rg1 could be a potential candidate drug to improve the behavioral deficits in AD via modulating the expression of the proteins (i.e., CPLX2, SYN2, and SNP25).

Implication of expression of osteopontin and its receptor integrin alphanubeta3 in the placenta in the development of preeclampsia.

To investigate the expression of osteopontin (OPN) and its receptor integrin alphanubeta3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and alphanubeta3 in the placenta of the pregnant women with preeclampsia and healthy pregnant women was detected by immunohistochemistry, Western blotting and RT-PCR. Our results showed that OPN and alphanubeta3 protein were expressed in the placenta from normal pregnant woman and those with preeclampsia. OPN was located in the placental syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and integrin alphanubeta3 was mainly expressed on the surface of trophoblast cells. Expression of OPN and integrin alphanubeta3 in the placental tissue from preeclampsia subjects was significantly lower than that from the control group (P<0.05). Compared with the control group, expression of OPN in the placental tissue from preeclampsia group was significantly lower (P<0.05) but there was no significant difference in the expression of alphanu and beta3 between the preeclampsia group and the controls. It is concluded that OPN and its receptor integrin alphanubeta3 may be involved in the pathogenesis of preeclampsia.

Implication of Expression of Osteopontin and Its Receptor Integrin αvβ3 in the Placenta in the Development of Preeclampsia / 华中科技大学学报（医学）（英德文版）

To investigate the expression of osteopontin (OPN) and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeelampsia,the expression of OPN and αvβ3 in the placenta of the pregnant women with preeclampsia and healthy pregnant women was detected by immunohistochemistry,Western blotting and RT-PCR. Our results showed that OPN and αvβ3 protein were expressed in the placenta from normal pregnant woman and those with preeclampsia. OPN was located in the placental syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and integrin αvβ3 was mainly expressed on the surface of trophoblast cells. Expression of OPN and integrin αvβ3 in the placental tissue from preeclampsia subjects was significantly lower than that from the control group (P＜0.05). Compared with the control group,expression of OPN in the placental tissue from preeclampsia group was significantly lower (P＜0.05) but there was no significant difference in the expression of αv and β3 between the preeclampsia group and the controls. It is concluded that OPN and its receptor integrin αvβ3 may be involved in the pathogenesis of preeclampsia.