Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an ageing environment that can be reprogrammed with a senescence‑associated secretory phenotype, which gradually promotes therapeutic resistance. Certain signalling pathways, such as the NF‑κB, Wnt and PI3K/AKT/mTOR pathways, regulate the tumour ageing microenvironment and induce the proliferation and progression of lymphoma cells. Therefore, targeting senescence‑related enzymes or their signal transduction pathways may overcome radiotherapy or chemotherapy resistance and enhance the efficacy of relapsed/refractory lymphoma treatments. Mechanisms underlying drug resistance in lymphomas are complex. The ageing microenvironment is a novel factor that contributes to drug resistance in lymphomas. In terms of clinical translation, some senolytics have been used in clinical trials on patients with relapsed or refractory lymphoma. Combining immunotherapy with epigenetic drugs may achieve better therapeutic effects; however, senescent cells exhibit considerable heterogeneity and lymphoma has several subtypes. Extensive research is necessary to achieve the practical application of senolytics in relapsed or refractory lymphomas. This review summarises the mechanisms of senescence‑associated drug resistance in lymphoma, as well as emerging strategies using senolytics, to overcome therapeutic resistance in lymphoma.

Background Ginseng red skin root syndrome (GRS) is one of the most common ginseng ( Panax ginseng Meyer) diseases. It leads to a severe decline in P. ginseng quality and seriously affects the P. ginseng industry in China. However, as a root disease, the characteristics of the GRS rhizosphere microbiome are still unclear. Methods The amplicon bacterial 16 S rRNA genes and fungal ITS (Internal Transcribed Spacer) regions Illumina sequencing technology, combined with microbial diversity and composition analysis based on R software, was used to explore the relationship between soil ecological environment and GRS. Results There were significant differences in the diversity and richness of soil microorganisms between the rhizosphere with different degrees of disease, especially between healthy P. ginseng (HG) and heavily diseased groups. The variation characteristics of microbial abundance in different taxa levels were analyzed. The interaction network of rhizosphere microorganisms of P. ginseng under GRS background was established. We also found that different P. ginseng rhizosphere microbial communities have multiple changes in stability and complexity through the established interaction network. Microbes closely related to potential pathogenic fungi were also identified according to the interaction network, which provided clues for looking for biological control agents. Finally, the Distance-based redundancy analysis (dbRDA) results indicated that total phosphorus (TP), available potassium (AK), available phosphorus (AP), catalase (CAT), invertase (INV) are the key factors that influence the microbial communities. Moreover, the content of these key factors in the rhizosphere was negatively correlated with disease degrees. Conclusions In this study, we comprehensively analyzed the rhizosphere characteristics of P. ginseng with different levels of disease, and explored the interaction relationship among microorganisms. These results provide a basis for soil improvement and biological control of field-grown in the future.

Background: Ginseng is deemed to be an effective anti-aging therapy. Evidence for differences in representative active ingredients and anti-aging effects between garden ginseng (GG) and ginseng under forest (FG) is insufficient. Purpose: The study was designed to systematically analyze the differences in the mechanistic protective effects of GG and FG on aging mice based on their compositional differences. Methods: The chemical ingredients in GG and FG were first determined. In vivo, D-galactose-induced aging mice were orally administered GG or FG (400 mg/kg/day) for 6 weeks. Behavioral parameters of mice were measured by the radial 8-arm maze, and the changes in body weight and organ indices were recorded. Blood, brain tissue, and feces were collected for biochemical analysis, histopathological staining, Western blotting, and 16S rDNA intestinal flora sequencing, respectively. Results: The absolute contents of total ginsenosides, polyphenols, crude polysaccharides, starch, and protein in GG were 0.71, 0.68, 1.15, 2.27, and 1.08 folds higher than those in FG, respectively; while FG exhibited a higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) but lower relative content of starch than GG. GG and FG improved hippocampal lesions and poor weight gain, organ indices, and behavioral indices, and prevented excessive oxidative stress and acetylcholinesterase activity in aging mice. What's more, GG and FG treatment ameliorated excessive apoptosis and inflammatory reaction in the aging brain by modulating apoptosis-related proteins, PI3K/AKT/mTOR pathway, and SIRT1/NF-kappa B pathway. GG and FG also restored the diversity and structure of gut microbiota, up-regulated the relative abundance of beneficial bacteria (e.g., Lactobacillus), and tended to exert key anti-aging effects via the microbiota-gut-brain axis. Notably, in vivo experiments confirmed that FG had a stronger anti-aging activity than GG. Conclusion: FG exerts a more powerful anti-aging effect than GG by regulating oxidative stress, apoptosis, inflammation, and the microbe-gut-brain axis, possibly relying on the higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) in FG.

Aging is an inevitable and complicated process involving many physiological changes. Screening of natural biologically active anti-aging substances is a current research hotspot. Phlorizin (PZ), an important dihydrochalcone phytoconstituent, has been demonstrated to have antioxidant and anti-tumor effects. In this paper, different doses of PZ (20 and 40 mg/kg) were used to research the protective effect on D-galactose (D-gal) induced aging mice. Following hematoxylin and eosin staining and by observing the hippocampus, we found that PZ alleviated the damage caused by D-gal in neuronal cells, while PZ enhanced the learning and memory abilities of aging mice in a radical eight-arm maze. In order to explain the reasons for these anti-aging effects, we tested the antioxidant enzyme activity and malonic dialdehyde concentration in mouse serum, liver, and brain tissue. The contents of proteins related to anti-inflammation and apoptosis in brain tissue were analyzed, and the gut microbiota was also analyzed. The results indicated that PZ improved antioxidant enzyme activity while significantly reducing the malonic dialdehyde content. Western blotting analysis suggested that PZ effectively alleviated neuro-apoptosis via regulating the expressions of Bax, Bcl-2, and caspase-3. PZ also exerted anti inflammation effects by regulating the interleukin-1 beta/inhibitor of nuclear factor kappa B alpha/nuclear factor kappa-light-chain-enhancer of activated B-cells signaling pathways in brain tissues. Importantly, PZ improved the structure and diversity of the gut microbiota, and the microbiota-gut-brain axis may hold a key role in PZinduced anti-aging effects. In conclusion, PZ can be used as a potential drug candidate to combat aging.

Taxifolin (TAX) is a hepatoprotective flavanol compound, which is severely limited by poor solubility and low bioavailability. Liposomes (Lips) are used as well-recognized drug carrier systems that improve the water solubility and bioavailability of drugs, but are easily damaged by gastric juice after oral administration, resulting in the release of drugs in the gastric juice. Therefore, it is important to find materials that modify liposomes and avoid the destruction of the liposomal phospholipid bilayer structure by the gastrointestinal environment. Taxifolin liposomes (TAX-Lips) were modified by polyvinylpyrrolidone-k30 (PVP-TAX-Lips) and manufactured using a thin-film hydration technique. Particle size (109.27 ± 0.50 nm), zeta potential (−51.12 ± 3.79 mV), polydispersity coefficient (PDI) (0.189 ± 0.007), and EE (84.7 ± 0.2%) of PVP-TAX-Lips were studied. In addition, the results of in vitro release experiments indicated that the cumulative release rates of TAX-Lips and PVP-TAX-Lips were 89.73 ± 5.18% and 65.66 ± 4.86% in the simulated gastric fluid after 24 h, respectively, while the cumulative release rates were 68.20 ± 4.98% and 55.66 ± 3.92% in the simulated intestinal fluid after 24 h, respectively. Moreover, PVP-TAX-Lips were able to reverse lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced acute liver injury (ALI) by inducing autophagy to inhibit the expression levels of the TLR4/NF-κB signaling pathway and inflammatory factors, which suggested that PVP-TAX-Lips played an important role in the prevention of ALI and also provided a promising drug delivery system for the application of TAX.

As a consumer product, black chokeberry (Aronia melanocarpa) is difficult to consume due to its pungent taste. It is mainly used in various food industries to produce a variety of juices, preserves, extracts, fruit teas and nutritional supplements. Traditionally, Potawatomi Native Americans used black chokeberry to treat colds, coughs and fever. It has been found to contain numerous active ingredients. Currently, there are many health and medical products that contain black chokeberry. The purpose of this review is to understand the nutritional benefits of black chokeberry and to explore its beneficial effects on biological systems in vitro, thereby emphasizing its therapeutic prospects.

In order to develop novel herbicides, a series of novel acylthiourea derivatives containing methylsulfone were synthesized and characterized by melting point, elemental analysis, infrared spectroscopy, mass spectrometry and H-1 NMR spectroscopy. Furthermore, the preliminary herbicidal activity of title compounds was determined against Echinochloa crusgal, Polypogon fugax, Digitaria adscendens, Brassica napus, Amaranthus retroflexus and Abutilon theophrasti. The results of the petri dish experiments showed that a small part of title compounds had a good inhibitory effect on Digitaria adscendens and Brassica napus. The results of the greenhouse herbicidal activity experiments indicated that the compounds 4p, 4 w and 4x exhibited more high herbicidal activity against Brassica napus and Digitaria adscendens than the commercial herbicide bensulfuron-methyl. Moreover, except for compound 4i , all test compounds performed well in crop safety evaluation. Next, acetohydroxyacid synthase (AHAS) enzyme activity experiments were carried out, and the results showed that compound 4x had the highest inhibition rate reaching 89.12%. Finally, in order to screen AHAS inhibitor, molecular docking was performed by using AHAS protein and target ligand molecules 4a-4x . The results of molecular docking were similar to bioassay experiments. Compound 4p, 4w and 4x were considered potential AHAS inhibitors. (C) 2021 Published by Elsevier B.V.

PURPOSE:Taxifolin is a kind of dihydroflavone and is usually used as a food additive and health food for its antioxidant, anti-inflammatory, and anti-tumor activities. The purpose of this research is to probe into the hepatoprotective activity and the molecular mechanism of taxifolin.MATERIALS AND METHODS:The liver fibrosis model was established by intraperitoneal injection of 5 mL/kg body weight of CCl4 (20% CCl4 peanut oil solution), and taxifolin was dissolved with 0.9% physiological saline and administered intragastrically to mice.RESULTS:The results indicated that CCl4-induced significantly increased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice. Histopathological examination showed severe hepatocyte necrosis and hepatic tissue lesion. Immunohistochemical staining and rt-PCR analysis demonstrated that the expressions of inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α were increased. These changes were significantly reversed when treated with taxifolin. In addition, TUNEL staining and Bcl-2/Bax pathway confirmed that taxifolin significantly inhibited hepatocyte apoptosis. Besides, the research confirmed that taxifolin also inhibited the activation of hepatic stellate cells and the production of extracellular matrix (ECM) by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways.CONCLUSION:Taxifolin inhibited inflammation, and attenuated CCl4-induced oxidative stress and cell apoptosis by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways, which might in part contributed to taxifolin anti-hepatic fibrosis, further demonstrating that taxifolin may be an efficient hepatoprotective agent.

Taxifolin in larch is an important natural active ingredient, which prevents and treats liver diseases and cardiovascular diseases, and has many health benefits and application values ​​such as anti-tumor, anti-virus, and anti-aging. However, the traditional extraction method is not conducive to the protection of the ecological environment, and also limits the industrial production of taxifolin from larch. Therefore, the purpose of this research is to establish a larch callus culture system and obtain taxifolin from callus. The shoots of the stem-tips of Larix olgensis were used as explants to be cultured. The light conditions, optimal medium and hormone ratio for callus induction were screened to evaluate the callus induction characteristics of larch and its influence on the accumulation of taxifolin. The results showed that: callus formation started on 28 ~ 51 days, and the best conditions for inducing callus were explored: 12 h/d light culture MS + 2,4-D 2 mg/L + 6-BA 1 mg/L + KT 0.1 mg/L; The callus induction rate was 50-80 %; The hormone combination with the highest accumulation of taxifolin was 6-BA 1 mg/L + NAA 0.1 mg/L, reaching 0.477 . In conclusion, this study revealed a suitable induction condition for larch callus culture and taxifolin accumulation.

Background Ginseng red skin root syndrome (GRS) is one of the most common ginseng diseases. It leads to a severe decline in ginseng quality and seriously affects the ginseng industry in China. However, as a root disease, the characteristics of GRS rhizosphere microbiome are still unclear. Methods The amplicon sequencing technology, combined with bioinformatics analysis, was used to explore the relationship between soil ecological environment and GRS. Results There were significant differences in the diversity and richness of soil microorganisms between the rhizosphere with different degrees of disease, especially between healthy ginseng (HG) and heavily diseased groups. We also found that bacterial communities underwent multiple changes between complex stability and simple instability in different ginseng rhizospheres through the established interaction networks. The GRS group also had more competition with each other and ecological niche separation than the HG group. The fungal community's stability decreased significantly in the early stages of the disease, followed by the formation of a stable and complex fungal community. The GRS groups significantly increased interspecies cooperation and ecological niche overlap in the fungal network than the HG group. Microbes closely related to potential pathogenic fungi were also identified according to the interaction network, which provided clues for looking for biological control agents. Finally, the Distance-based redundancy analysis (dbRDA) results indicated that total P (TP), available K (AK), available P (AP), catalase (CAT), invertase (INV) are the key factors that influence the microbial communities. Conclusions This study collectively analyzed the changing characteristics in ginseng rhizosphere and provided the basis for soil improvement and biological control of field-grown ginseng.

BACKGROUND:Panax ginseng (PG) and red ginseng (RG) are considered to be effective anti-aging treatments. However, evidence of their therapeutic mechanisms and difference in anti-aging effects is lacking. PURPOSE:To explore the potential therapeutic mechanisms of RG and PG in brain damage in D-Gal-induced aging mice, and evaluate the difference in anti-aging effects caused by their compositional differences. METHODS:We first tested the chemical components in PG and RG. In D-Gal aging mouse model, RG and PG (800 mg/kg) were orally administered for 9 weeks. The mice performed the Radial Arm Maze (RAM) behavior test. We collected blood, brain tissue, and fecal samples and performed biochemical analysis, histological examination, western blot, and Illumina MiSeq sequencing analysis. RESULTS:The results of component analysis showed that the total polyphenols and rare ginsenosides were present in RG in 3.2, and 2.2 fold greater concentrations, respectively, compared to PG, while the proportion of non-starch polysaccharides in the crude polysaccharides of RG was 1.94 fold greater than that of PG. In D-Gal-induced aging mice, both PG and RG could prevent the increase in acetylcholinesterase (AChE), and malondialdehyde (MDA) levels, and improved the expression of superoxide dismutase (SOD), and catalase (CAT) in the serum. Meanwhile, both PG and RG could ameliorate brain tissue architecture and behavioral trial. In addition, the D-Gal-induced translocation of nuclear factor-κB (NF-κB), as well as activation of the pro-apoptotic factors Caspase-3 and the PI3K/Akt pathways were inhibited by PG and RG. Overall, both PG and RG exerted anti-aging effects, with RG stronger than PG. Finally, although both PG and RG regulated the diversity of gut microbes, RG appeared to aggravate the increase in probiotics, such as Bifidobacterium and Akkermania, and the decrease in inflammatory bacteria to a greater extent compared to PG. CONCLUSION:Our results suggest that RG is more conducive to delay the D-Gal-induced aging process than PG, with possible mechanisms including beneficial changes in brain structure, cognitive functions, oxidative stress inhibition, and gut microbiome structure and diversity than PG, These mechanisms may rely on the presence of more total polyphenols, rare ginsenosides and non-starch polysaccharides in RG.

Ginseng rusty root symptom (GRS) is one of the primary diseases of ginseng. It leads to a severe decline in the quality of ginseng and significantly affects the ginseng industry. The regulatory mechanism of non-coding RNA (ncRNA) remains unclear in the course of disease. This study explored the long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in GRS tissues and healthy ginseng (HG) tissues and performed functional enrichment analysis of the screened differentially expressed ncRNAs. Considering the predictive and regulatory effects of ncRNAs on mRNAs, we integrated ncRNA and mRNA data to analyze and construct relevant regulatory networks. A total of 17,645 lncRNAs, 245 circRNAs, and 299 miRNAs were obtained from HG and GRS samples, and the obtained ncRNAs were characterized, including the classification of lncRNAs, length and distribution of circRNA, and the length and family affiliations of miRNAs. In the analysis of differentially expressed ncRNA target genes, we found that lncRNAs may be involved in the homeostatic process of ginseng tissues and that lncRNAs, circRNAs, and miRNAs are involved in fatty acid-related regulation, suggesting that alterations in fatty acid-related pathways may play a key role in GRS. Besides, differentially expressed ncRNAs play an essential role in regulating transcriptional translation processes, primary metabolism such as starch and sucrose, and secondary metabolism such as alkaloids in ginseng tissues. Finally, we integrated the correlations between ncRNAs and mRNAs, constructed corresponding interaction networks, and identified ncRNAs that may play critical roles in GRS. These results provide a basis for revealing GRS's molecular mechanism and enrich our understanding of ncRNAs in ginseng.

Breast cancer is one of the most common malignant tumors among women worldwide and has a high morbidity and mortality. This research aimed to identify hub genes and small molecule drugs for breast cancer by integrated bioinformatics analysis. After downloading multiple gene expression datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, 283 overlapping differentially expressed genes (DEGs) significantly enriched in different cancer-related functions and pathways were obtained using LIMMA, VennDiagram and ClusterProfiler packages of R. We then analyzed the topology of protein–protein interaction (PPI) network with overlapping DEGs and further obtained six hub genes (RRM2, CDC20, CCNB2, BUB1B, CDK1, and CCNA2) from the network via STRING and Cytoscape. Subsequently, we conducted genes expression verification, genetic alterations evaluation, immune infiltration prediction, clinicopathological parameters analysis, identification of transcriptional and post-transcriptional regulatory molecules, and survival analysis for these hub genes. Meanwhile, 29 possible drug candidates (e.g., Cladribine, Gallium nitrate, Alvocidib, 1β-hydroxyalantolactone, Berberine hydrochloride, Nitidine chloride) were identified from the DGIdb database and the GSE85871 dataset. In addition, some transcription factors and miRNAs (e.g., E2F1, PTTG1, TP53, ZBTB16, hsa-miR-130a-3p, hsa-miR-204-5p) targeting hub genes were identified as key regulators in the progression of breast cancer. In conclusion, our study identified six hub genes and 29 potential drug candidates for breast cancer. These findings may advance understanding regarding the diagnosis, prognosis and treatment of breast cancer.

The purpose of this study was to determine whether abscisic acid (ABA) can protect against liver fibrosis induced by thioacetamide (TAA) in vivo by inhibiting apoptosis and inflammatory responses. To this end, three times per week, mice were injected intraperitoneally with TAA (200 mg/kg) for 8 weeks to induce liver fibrosis. After the fourth week of treatment, histological changes, the serum biochemical index, inflammation, and hepatocyte apoptosis factors (e.g., caspase-3, B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X [Bax]) were detected to clarify its underlying mechanism. The results clearly indicated that ABA improves TAA-induced hepatic injury and collagen accumulation in mice. Otherwise, ABA significantly reduced liver fibrosis by regulating caspase-3 and Bcl-2, α-smooth muscle actin, and collagen I. ABA inhibited the nuclear factor kappa B pathway, significantly alleviating oxidative stress and inflammatory cytokines. Therefore, ABA may be a potential therapeutic agent for preventing liver damage.