Long-term Effect of Hematopoietic Stem Cell Transplantation on the Quality of Life of Patients with ß-thalassemia Major in Guangxi, China - A Cross-sectional Study.

OBJECTIVE: The purpose of our study was to compare the quality of life (QOL) of patients with hematopoietic stem cell transplantation (HSCT) for more than 2 years for ß -thalassemia major (ß-TM) with that of ß-TM patients with conventional therapy (blood infusion and iron chelation) and that of the general population. METHODS: This was a cross-sectional comparative study on the QOL of 225 ß-TM patients treated with blood transfusion and iron chelation therapy, 133 ß-TM patients who had undergone HSCT or 270 ageand sex-matched healthy individuals from Guangxi, China. Child-self and parent-proxy reports of the PedsQL 4.0 Generic Core Scales were used to prospectively evaluate QOL. RESULTS: The incidence of acute GVHD was 14.3% (grade III-IV in 4.5% of patients), and that of chronic GVHD was 3.8%. This was lower than that of previous studies since the inclusion of anti-thymocyte globulin (ATG). Patients who underwent transplantation from a voluntary donor had higher QOL scores and lower rates of acute GVHD, chronic GVHD and comorbidities than those receiving stem cell sources from an HLA mismatched related donor (haploidentical donor). Transplants with PBSCs or UCBT, PBSCT+BMT, BMT, or BMT+UCBT as stem cell sources did not have any impact on QOL. The QOL of ß-TM patients was very similar to that of the general population. More complications (P<0.001), shorter post-transplantation time (P<0.001), and older age at HSCT (P=0.01) were associated with poorer child QOL (P=0.020). Additional analyses investigating QOL of ß-TM patients receiving conventional treatment with ß-TM revealed poorer outcomes than the cohort of transplanted patients. CONCLUSION: ß-TM patients can be cured by HSCT and regain QOL as good as that of the general population. ß-TM patients are suggested to undergo HSCT as soon as possible to avoid complications related to iron overload and blood infusion.

Panax ginseng Meyer cv. Silvatica phenolic acids protect DNA from oxidative damage by activating Nrf2 to protect HFF-1 cells from UVA-induced photoaging.

ETHNOPHARMACOLOGICAL RELEVANCE: Long-wave ultraviolet A (UVA) causes skin aging by damaging the fine structures of the skin, such as elastic fibers and collagen fibers, through oxidation. Currently, the use of plant extracts to protect skin from photoaging is a popular method. Panax ginseng C.A. Meyer exerts commendable anti-photoaging and antioxidant effects. P. ginseng Meyer cv. Silvatica, also known as forest ginseng (FG), is a type of ginseng cultivated by artificially simulating the growth environment of wild ginseng aged >15 years. However, there are only a few reports on its anti-photoaging effect on the skin caused by UVA stimulation. AIM OF THE STUDY: To investigate whether isolated and extracted FG can inhibit skin photoaging as well as to explore its action mechanism. METHODS: The FG extract (FGE) was obtained from the supernatant of FG after water extraction and alcohol precipitation with the D101 resin. The composition and content of phenolic acids in FGE were determined by high-performance liquid chromatography (HPLC). The MTT assay was performed to detect cell viability. The ratio of SA-ß-GAL-positive cells, CoL-I level, 8-OHdG concentration, MDA, GSH, GPx, SOD, and CAT activity were measured using relevant kits. Furthermore, cell cycle alterations and ROS accumulation were assessed by flow cytometry. The expressions of p53, p21, p16, and Keap1 protein were detected by Western blotting. The Nrf2 translocation was monitored by immunofluorescence staining. RESULTS: The findings revealed that FGE significantly restored UVA injury-induced cell viability, reduced the proportion of SA-ß-GAL-positive cells, and increased the level of CoL-I secretion in a dose-dependent manner, where the main ingredients were chlorogenic acid, protocatechuic acid, salicylic acid, p-hydroxybenzoic acid, vanillic acid, ferulic acid, and caffeic acid. Further studies indicated that this phenolic acid mixture (PAM) could alleviate UVA-induced HFF-1 cell cycle arrest and protect the DNA from oxidative damage caused by UVA stimulation. Moreover, the expressions of cell cycle regulatory proteins p53, p21, and p16 and the accumulation of ROS were inhibited, the translocation of Nrf2 into the nucleus was promoted, the expression of Keap1 protein was inhibited, the activity of intracellular antioxidant indicators GSH, GPx, SOD, and CAT was enhanced, and the expression of malondialdehyde (MDA) was inhibited. CONCLUSIONS: Collectively, our results demonstrated that FG phenolic acids protect DNA from oxidative damage by activating Nrf2 to safeguard the skin from photoaging induced by UVA stimulation.

Underlying Mechanism and Active Ingredients of Tianma Gouteng Acting on Cerebral Infarction as Determined via Network Pharmacology Analysis Combined With Experimental Validation.

Cerebral infarction (CI), a common cerebrovascular disease worldwide, is caused by unknown factors common to many diseases, including hypokalemia, respiratory diseases, and lower extremity venous thrombosis. Tianma Gouteng (TMGT), a traditional Chinese Medicine (TCM) prescription, has been used for the clinical treatment of CI. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis was used to detect and identify major chemical constituents of TMGT. TCMSP and BATMAN-TCM databases were used to screen for active TMGT constituent compounds, while the GeneCards database was used to screen for protein targets associated with CI. Next, GO and KEGG enrichment analysis of these core nodes were performed to determine the identities of key associated biological processes and signal pathways. Meanwhile, a total of six possible gene targets of TMGT, including NFKBIA, PPARG, IL6, IL1B, CXCL8, and HIF1A, were selected for further study using two cellular models of CI. For one model, PC12 cells were treated under oxygen and glucose deprivation (OGD) conditions to generate an OGD cellular model of CI, while for the other model, BV2 cells were stimulated with lipopolysaccharide (LPS) to generate a cellular model of CI-associated inflammation. Ultimately TMGT treatment increased PPARγ expression and downregulated the expression of p-P65, p-IκBα, and HIF-1α in both OGD-induced and LPS-induced cell models of CI. In addition, molecular docking analysis showed that one TMGT chemical constituent, quercetin, may be a bioactive TMGT compound with activity that may be associated with the alleviation of neuronal damage and neuroinflammation triggered by CI. Moreover, additional data obtained in this work revealed that TMGT could inhibit neuroinflammation and protect brain cells from OGD-induced and LPS-induced damage by altering HIF-1α/PPARγ/NF-κB pathway functions. Thus, targeting this pathway through TMGT administration to CI patients may be a strategy for alleviating nerve injury and neuroinflammation triggered by CI.

Ginsenoside extract from ginseng extends lifespan and health span in Caenorhabditis elegans.

Nutrition intervention has become a potential strategy to improve healthspan and prolong lifespan. Ginseng has been used for thousands of years and developed as a functional food to provide various protective effects to humans. An extract of total ginsenosides (TGS), a mixture of the main active ginsenosides from ginseng, has wide biological activities and health benefits for age-related diseases, including antioxidation and improvements in mitochondrial function. However, the molecular mechanism of TGS for prolonging lifespan and improving fitness and how exactly this is achieved under normal and stress conditions remain largely unclear. In this study, wild-type and mutant C. elegans strains are used to investigate the role and molecular mechanism of TGS-mediated longevity, health benefits, and stress resistance. The results showed that treatment with TGS at 0.2 mg mL-1 from the stage of day four to death significantly extended the lifespan of worms by 14.02% without effects on bacterial metabolism and food intake. Furthermore, TGS treatment obviously improved age-associated mobility, muscle fiber organization, lipofuscin accumulation, and enhanced resistance under oxidative stress. Importantly, these effects of TGS were achieved by activating the signaling pathways of anti-oxidant regulation and longevity, including the NRF2/SKN-1, SIRT1/SIR 2.1, and FOXO/DAF-16 signaling pathways. Finally, it was found that Rg1, Re, and Rb1 were the major effective components of anti-oxidative activity and longevity. Collectively, the protective effect of ginsenoside extract in healthy aging and stress responses provides new insights for the development and practical application of ginseng functional products.

Panax notoginseng Saponins Promote Cell Death and Chemosensitivity in Pancreatic Cancer through the Apoptosis and Autophagy Pathways.

BACKGROUND: Panax notoginseng Saponins (PNS) is used as a traditional Chinese medicine for ischemic stroke and cardiovascular disease; it has been proven to possess anticancer activity recently. OBJECTIVE: In this study, we aimed to explore the curative anticancer effect and potential mechanisms of PNS in pancreatic cancer cells. METHODS: Pancreatic cancer Miapaca2 and PANC-1 cells were treated with PNS and Gemcitabine (Gem), respectively. Then the cell viability was assessed by CCK-8 assay, cell proliferation was tested by colony formation assay and EdU cell proliferation assay, cell migration and invasiveness were tested by wound healing assay and transwell assay, respectively, and cell apoptosis was detected by flow cytometry. Finally, we detected the expression levels of proteins related to migration, apoptosis and autophagy through Western blotting. RESULTS: PNS not only inhibited the proliferation, migration, invasion and autophagy of Miapaca2 and PANC-1 cells, but also induced apoptosis and promoted chemosensitivity of pancreatic cancer cells to Gem. CONCLUSION: PNS may exhibit cytotoxicity and increase chemosensitivity of pancreatic cancer cells to Gem by inhibiting autophagy and inducing apoptosis, providing a new strategy and potential treatment option for pancreatic cancer.

Shen-Hong-Tong-Luo Formula Attenuates Macrophage Inflammation and Lipid Accumulation through the Activation of the PPAR-γ/LXR-α/ABCA1 Pathway.

Atherosclerosis (AS) is the killer of human health and longevity, which is majorly caused by oxidized lipoproteins that attack macrophages in the endarterium. The Shen-Hong-Tong-Luo (SHTL) formula has shown great clinical efficacy and vascular protective effect for over 30 years in China, to attenuate AS progression. However, its pharmacological mechanism needs more investigation. In this study, we first investigated the chemical composition of SHTL by fingerprint analysis using high-performance liquid chromatography. In primary mouse peritoneal macrophages induced by lipopolysaccharide (LPS), we found that SHTL pretreatment suppressed reactive oxygen species accumulation and reversed the increases of the inflammatory factors, TNF-α and IL-6. Moreover, lipid accumulation induced by oxidized low-density lipoprotein (Ox-LDL) in macrophages was inhibited by SHTL. Additionally, network pharmacology was used to predict the potential targets of SHTL as the PPAR-γ/LXR-α/ABCA1 signaling pathway, which was validated in macrophages and ApoE-/- mice by histopathological staining, qPCR, and Western blot analysis. Importantly, the protective effect of SHTL in the LPS- and Ox-LDL-induced macrophages against inflammation and lipid accumulation was attenuated by GW9662, a PPAR-γ antagonist, which confirmed the prediction results of network pharmacology. In summary, these results indicated that SHTL pretreatment reduced inflammation and lipid accumulation of macrophages by activating the PPAR-γ/LXR-α/ABCA1 pathway, which may provide a new insight into the mechanism of SHTL in the suppression of AS progression.

Efficient Hydrolysis of Raw Microalgae Starch by an α-Amylase (AmyP) of Glycoside Hydrolase Subfamily GH13_37.

Microalgae starch is receiving increasing attention as a renewable feedstock for biofuel production. Raw microalgae starch from Tetraselmis subcordiformis was proven to be very efficiently hydrolyzed by an α-amylase (AmyP) of glycoside hydrolase subfamily GH13_37 below the temperature of gelatinization (40 °C). The hydrolysis degree reached 74.4 ± 2.2% for 4% raw microalgae starch and 53.2 ± 1.7% for 8% raw microalgae starch after only 2 h. The hydrolysis efficiency was significantly stimulated by calcium ions. The enzyme catalysis of AmyP and its mutants (Q306A and E347A) suggested that calcium ions contributed to the hydrolysis of cyclic structures in raw microalgae starch by a distinctive calcium-binding site Ca2 of AmyP. The study explored raw microalgae starch as a new resource for cold enzymatic hydrolysis and extended our knowledge on the function of calcium in amylolytic enzyme.