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International Journal of Molecular... Nov 2023No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this... (Review)
Review
No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.
Topics: Rats; Mice; Animals; Peripheral Nerve Injuries; Melatonin; Prospective Studies; Retrospective Studies; Peripheral Nerves; Sciatic Nerve; Nerve Regeneration; Autophagy
PubMed: 38003409
DOI: 10.3390/ijms242216219 -
International Journal of Molecular... Aug 2023Sepsis is associated with high rates of mortality in the intensive care unit and accompanied by systemic inflammatory reactions, secondary infections, and multiple organ... (Review)
Review
Sepsis is associated with high rates of mortality in the intensive care unit and accompanied by systemic inflammatory reactions, secondary infections, and multiple organ failure. Biological macromolecules are drugs produced using modern biotechnology to prevent or treat diseases. Indeed, antithrombin, antimicrobial peptides, interleukins, antibodies, nucleic acids, and lentinan have been used to prevent and treat sepsis. In vitro, biological macromolecules can significantly ameliorate the inflammatory response, apoptosis, and multiple organ failure caused by sepsis. Several biological macromolecules have entered clinical trials. This review summarizes the sources, efficacy, mechanism of action, and research progress of macromolecular drugs used in the prevention and treatment of sepsis.
Topics: Humans; Multiple Organ Failure; Sepsis; Antibodies; Anticoagulants; Antimicrobial Peptides; Macromolecular Substances
PubMed: 37629199
DOI: 10.3390/ijms241613017 -
European Journal of Medical Research Jan 2024Shiitake mushrooms are a fungal food that has been recorded in Chinese medicine to nourish the blood and qi. Lentinan (lLNT) is an active substance extracted from... (Review)
Review
Shiitake mushrooms are a fungal food that has been recorded in Chinese medicine to nourish the blood and qi. Lentinan (lLNT) is an active substance extracted from shiitake mushrooms with powerful antioxidant, anti-inflammatory, anti-tumor functions. Inflammatory diseases and cancers are the leading causes of death worldwide, posing a serious threat to human life and health and posing enormous challenges to global health systems. There is still a lack of effective treatments for inflammatory diseases and cancer. LNT has been approved as an adjunct to chemotherapy in China and Japan. Studies have shown that LNT plays an important role in the treatment of inflammatory diseases as well as oncological diseases. Moreover, clinical experiments have confirmed that LNT combined with chemotherapy drugs has a significant effect in improving the prognosis of patients, enhancing their immune function and reducing the side effects of chemotherapy in lung cancer, colorectal cancer and gastric cancer. However, the relevant mechanism of action of the LNT signaling pathway in inflammatory diseases and cancer. Therefore, this article reviews the mechanism and clinical research of LNT in inflammatory diseases and tumor diseases in recent years.
Topics: Humans; Lentinan; Stomach Neoplasms; Lung Neoplasms; Treatment Outcome; Prognosis
PubMed: 38172925
DOI: 10.1186/s40001-023-01585-7 -
Biomedicine & Pharmacotherapy =... Nov 2023Diabetic cardiomyopathy (DCM), characterized by mitochondrial dysfunction and impaired energetics as contributing factors, significantly contributes to high mortality in...
Diabetic cardiomyopathy (DCM), characterized by mitochondrial dysfunction and impaired energetics as contributing factors, significantly contributes to high mortality in patients with diabetes. Targeting key proteins involved in mitochondrial dysfunction might offer new therapeutic possibilities for DCM. Lentinan (LNT), a β-(1,3)-glucan polysaccharide obtained from lentinus edodes, has demonstrated biological activity in modulating metabolic syndrome. In this study, the authors investigate LNT's pharmacological effects on and mechanisms against DCM. The results demonstrate that administering LNT to db/db mice reduces cardiomyocyte apoptosis and mitochondrial dysfunction, thereby preventing DCM. Notably, these effects are fully negated by Caveolin-1 (CAV1) overexpression both in vivo and in vitro. Further studies and bioinformatics analysis uncovered that CAV1 bound with Succinate dehydrogenase subunit A (SDHA), triggering the following ubiquitination and degradation of SDHA, which leads to mitochondrial dysfunction and mitochondria-derived apoptosis under PA condition. Silencing CAV1 leads to reduced apoptosis and improved mitochondrial function, which is blocked by SDHA knockdown. In conclusion, CAV1 directly interacts with SDHA to promote ubiquitination and proteasomal degradation, resulting in mitochondrial dysfunction and mitochondria-derived apoptosis, which was depressed by LNT administration. Therefore, LNT may be a potential pharmacological agent in preventing DCM, and targeting the CAV1/SDHA pathway may be a promising therapeutic approach for DCM.
Topics: Mice; Animals; Humans; Diabetic Cardiomyopathies; Lentinan; Caveolin 1; Mitochondria; Diabetes Mellitus; Electron Transport Complex II
PubMed: 37804808
DOI: 10.1016/j.biopha.2023.115645 -
Journal of Fungi (Basel, Switzerland) Feb 2024Medicinal mushrooms are multicomponent mixtures (MOCSs). They consist of a large number of individual compounds, each with different chemical structures, functions, and... (Review)
Review
Medicinal mushrooms are multicomponent mixtures (MOCSs). They consist of a large number of individual compounds, each with different chemical structures, functions, and possible pharmacological activities. In contrast to the activity of an isolated pure substance, the effects of the individual substances in a mushroom or its extracts can influence each other; they can strengthen, weaken, or complement each other. This results in both advantages and disadvantages for the use of either a pure substance or a multicomponent mixture. The review describes the differences and challenges in the preparation, characterization, and application of complex mixtures compared to pure substances, both obtained from the same species. As an example, we use the medicinal and culinary mushroom , shiitake, and some of its isolated compounds, mainly lentinan and eritadenine.
PubMed: 38392825
DOI: 10.3390/jof10020153 -
Oncology Reports Jul 2023Lentinan (LNT) isolated from is a vital host defense potentiator previously utilized as an adjuvant in cancer therapy. The present study investigated the effect of LNT...
Lentinan (LNT) isolated from is a vital host defense potentiator previously utilized as an adjuvant in cancer therapy. The present study investigated the effect of LNT on the mouse hepatocellular carcinoma (HCC) cell line Hepa1‑6 and its possible mechanism. Mouse HCC apoptosis and its potential associated mechanism were then explored using and approaches. For approaches, the effect of LNT on the proliferation of Hepa1‑6 cells was investigated by Cell Counting Kit‑8 assay. Annexin V‑FITC staining and flow cytometry were applied to explore HCC apoptosis. Western blotting was used to analyze related proteins, such as EGR1, phosphatase and tensin homolog (PTEN), phosphorylated protein kinase B (p‑Akt), protein kinase B (Akt), B lymphocyte‑2 (Bcl‑2), Bcl2 family‑associated X protein (Bax), etc. Cellular immunofluorescence staining was employed to assess the localization and expression of EGR1 and PTEN in nuclear and cytoplasmic fractions of Hepa1‑6 cells. The association between and was explored by overexpression in cell lines. For methods, a mouse model of diethylnitrosamine (DEN)‑induced primary liver cancer was established using C57BL/6 mice to investigate the inhibitory effect of LNT on liver cancer. Histopathology of liver tissue from mice was detected by hematoxylin‑eosin staining and immunohistochemical assay. and results showed that LNT can inhibit the proliferation and promote the apoptosis of mouse HCC cells. Besides, LNT increased the expression of EGR1 in Hepa1‑6 cells, which is translocated to the nucleus to function as a transcriptional factor. EGR1 then activates the expression of the tumor suppressor PTEN, thereby inhibiting the activation of the AKT signaling pathway. These data revealed a novel anti‑tumor mechanism by which LNT can induce apoptosis to inhibit mouse HCC progression through the EGR1/PTEN/AKT axis. These results provide a scientific basis for the potential use of LNT in drug development and clinical applications associated with primary liver cancer.
Topics: Mice; Animals; Proto-Oncogene Proteins c-akt; Carcinoma, Hepatocellular; Lentinan; Liver Neoplasms; Cell Line, Tumor; Mice, Inbred C57BL; Mice, Inbred Strains; Signal Transduction; Apoptosis; PTEN Phosphohydrolase; Cell Proliferation; Early Growth Response Protein 1
PubMed: 37264970
DOI: 10.3892/or.2023.8579 -
Frontiers in Pharmacology 2023Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that...
Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that lentinan nasal drops can assist [Corona Virus Disease 2019) COVID-19] vaccine to induce high levels of neutralizing antibodies and can effectively resist the invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the safety and efficacy of lentinan nasal drops in patients infected with Omicron (SARS-CoV-2 variant) through a dose-escalation study and a placebo-controlled trial. A randomized, placebo-controlled trial. The study was divided into two phases: Phase I: a dose escalation trial in which 24 COVID-19 patients were enrolled, that is, 12 in the escalation dose group (50, 75, and 100 µg/day) and 12 in the standard treatment group. The aim was to evaluate the safety and tolerance of lentinan nasal drops. The second stage was a placebo-controlled study. The optimal dose group of the first stage was used as the therapeutic dose, and the sample size was expanded to verify the anti-COVID-19 efficacy of lentinan nasal drops. In the dose-increasing study, lentinan nasal drops showed good safety, and no serious adverse reactions occurred. The virus shedding time of the 100 µg dose group was significantly shorter than that in the control group (7.75 ± 1.71 VS 13.41 ± 3.8 days) ( = 0.01), and the 100 µg/day lentinan nasal drops were tolerated well. The results of the placebo-controlled study showed that compared with that in the placebo group, the time for COVID-19 antigen to turn negative was significantly shorter in the 100 µg lentinan nasal drop group ( = 0.0298), but no significant difference was observed in symptom improvement between the two groups. In the placebo-controlled study, two patients experienced mild nasal discomfort with nasal drops, but the symptoms relieved themselves. Lentinan nasal drops are tolerated well and can shorten the time of virus clearance.
PubMed: 38108068
DOI: 10.3389/fphar.2023.1292479 -
Ecotoxicology and Environmental Safety Oct 2023Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs...
Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs through oxidative stress. The development of natural extracts that can reduce oxidative damage is a promising method. Lentinan is isolated from Lentinus edodes and has been verified its antioxidant activity. In this study, Caenorhabditis elegans was used to evaluate the protective effects of lentinan against fluopyram-induced toxicity and the possible mechanisms. Results showed that lentinan pretreatment notably increased the survival rate of N2 nematodes by 15.0 % and extended the lifespan by 91.5 %, compared with the fluopyram treatment. Lentinan pretreatment reverted the inhibition of the locomotion and reproduction of C. elegans under the fluopyram stress. In addition, lentinan pretreatment significantly decreased the contents of ROS and MDA in N2 nematodes. Moreover, pretreated with lentinan significantly recovered the decreased activities of CAT, SOD, GST and SDH induced by fluopyram. Lentinan pretreatment enhanced the mRNA levels of daf-16 and skn-1 and their downstream genes in the nematodes compared with the fluopyram group. In daf-16 and skn-1 mutants, the lifespan, ROS and related genes expression were not significantly changed in lentinan pretreatment. Pretreated with lentinan significantly enhanced the fluorescence intensity of SOD-3::GFP and GST-4::GFP, and promoted the nuclear translocation of DAF-16 and SKN-1 under the fluopyram stress. In summary, these findings indicated that lentinan protected C. elegans from fluopyram-induced toxicity via DAF-16 and SKN-1.
PubMed: 37742572
DOI: 10.1016/j.ecoenv.2023.115510 -
Animals : An Open Access Journal From... Apr 2024In this study, we investigated the effects of lentinan (LNT) on hematological parameters, immune indices, and metabolite levels in dairy cows. We randomly assigned forty...
In this study, we investigated the effects of lentinan (LNT) on hematological parameters, immune indices, and metabolite levels in dairy cows. We randomly assigned forty Holstein cows to four treatment groups. The treatments consisted of 0, 5, 10, and 15 g/d of LNT. Compared with the control group, the addition of 10 g/d of LNT decreased the content of ALT and IL-8 but simultaneously increased the content of IL-4 in the cows' serum. Supplementation with 10 g/d of LNT decreased the levels of lymphocyte, RDW, ALT, AST, TC, IL-2, and IL-8, but, concurrently, in-creased the levels of granulocytes and IL-4 in their serum. In addition, supplementation with 15 g/d of LNT decreased the levels of RDW, TC, IL-2, and IL-8, but, at the same time, increased the levels of IL-4 and IgM in their serum. For the metabolomic analysis, cows fed with 0 and 10 g/d of LNT were selected. The results showed that 10 metabolites, including reduced nicotinamide riboside and trehalose, were upregulated in the 10 g/d group. These differential metabolites were enriched in tyrosine metabolism and trehalose degradation and altered two metabolic pathways of ubiquinone and other terpene quinone biosynthesis, as well as starch and sucrose metabolism. These findings provide evidence that LNT could be used to reduce the risk of inflammation in dairy cows.
PubMed: 38731317
DOI: 10.3390/ani14091314 -
Parasites & Vectors Dec 2023Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of...
BACKGROUND
Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice.
METHODS
A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively.
RESULTS
Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth.
CONCLUSIONS
Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.
Topics: Animals; Mice; Lentinan; Toxoplasmosis; Brain; Toxoplasma; Neurodegenerative Diseases; Cognition
PubMed: 38093309
DOI: 10.1186/s13071-023-06023-5