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BACKGROUND: Schisandra chinensis (Turcz.) Baill, a fruit utilized in traditional Chinese medicine (TCM), has a long history of medical application. It has been used to treat diseases of the gastrointestinal tract. Schisandra chinensis (Turcz.) Baill polysaccharide (SACP) is an important biologically active ingredient that has been shown to have a variety of beneficial effects including immune regulation and anti-oxidative properties. Ulcerative colitis (UC) is a complicated gastrointestinal inflammatory disease. We explore the protective effect of SACP against UC. RESULTS: Schisandra chinensis (Turcz.) Baill polysaccharide significantly reduced the disease activity index (DAI) and levels of myeloperoxidase(MPO) and malondialdehyde (MDA) in colonic tissue. It also alleviated weight loss and histopathological damage of mice. The expression of MUC2 and occludin proteins was increased and the barrier function of the colonic mucosa was enhanced by SACP treatment. NF-κB pathway activation was also inhibited and the production of pro-inflammatory cytokines was decreased whereas anti-inflammatory cytokines were increased. 16SrDNA sequencing of fecal flora showed that SACP increased the abundance of Muribaculaceaeunclassified, LachnospiraceaeNK4A136group and reduced the abundance of Bacteroides and Erysipelatoclostridium. CONCLUSION: Schisandra chinensis (Turcz.) Baill polysaccharide can protect against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis in mice. © 2023 Society of Chemical Industry.
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Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Schisandra , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , NF-kappa B/genética , NF-kappa B/metabolismo , Schisandra/química , Schisandra/metabolismo , Polissacarídeos , Colo/metabolismo , Citocinas/metabolismo , Cloreto de Sódio , Sulfato de Dextrana/efeitos adversos , Modelos Animais de DoençasRESUMO
Cancer, a serious fatal disease caused by the uncontrolled growth of cells, is the biggest challenge flagging around medicine and health fields. Conventionally, various treatments-based strategies such as radiotherapy, chemotherapy, and alternative cancer therapies possess drugs that cannot reach the cancerous tissues and make them toxic to noncancerous cells. Cancer immunotherapy has made outstanding achievements in reducing the chances of cancer. Our considerable attention towards cancer-directed immune responses and the mechanisms behind which immune cells kill cancer cells have progressively been helpful in the advancement of new therapies. Among them, bacteria-based cancer immunotherapy has achieved much more attention due to smart and robust mechanisms in activating the host anti-tumor response. Moreover, bacterial-based therapy can be utilized as a single monotherapy or in combination with multiple anticancer immunotherapies to accelerate productive clinical results. Herein, we comprehensively reviewed recent advancements, challenges, and future perspectives in developing bacterial-based cancer immunotherapies.
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Cardiovascular diseases (CVDs) are one of the leading disorders of serious death and cause huge economic loss to patients and society. It is estimated that about 18 million people have a high death ratio due to the incidence of CVDs such as (stroke, coronary heart disease, and non-ischemic heart failure). Bioactive compounds (BACs) are healthy nutritional ingredients providing beneficial effects and nutritional value to the human body. Epidemiological studies strongly shed light on several bioactive compounds that are favorable candidates for CVDs treatment. Globally, the high risk of CVDs and related results on human body parts made them a serious scenario in all communities. In this present review, we intend to collect previously published data concerned over the years concerning green-colored foods and their BACs that aim to work in the prevention, diagnosis, and/or systematic treating CVDs. We also comprehensively discussed the oral delivery of several bioactive compounds derived from fruits and vegetables and their bioavailability and physiological effects on human health. Moreover, their important characteristics, such as anti-inflammatory, lowering blood pressure, anti-obesity, antioxidant, anti-diabetics, lipid-lowering responses, improving atherosclerosis, and cardio protective properties, will be elaborated further. More precisely, medicinal plants' advantages and multifaceted applications have been reported in this literature to treat CVDs. To the best of our knowledge, this is our first attempt that will open a new window in the area of CVDs with the opportunity to achieve a better prognosis and effective treatment for CVDs.
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Doenças Cardiovasculares , Doença das Coronárias , Insuficiência Cardíaca , Humanos , Doenças Cardiovasculares/epidemiologia , Frutas , Anti-InflamatóriosRESUMO
Cardiovascular diseases (CVDs) are the leading cause of death around the world, a trend that will progressively grow over the next decade. Recently, with the advancement of nanotechnology, innovative nanoparticles (NPs) have been efficiently utilized in disease diagnosis and theranostic applications. In this review, we highlighted the benchmark summary of the recently synthesized NPs that are handy for imaging, diagnosis, and treatment of CVDs. NPs are the carrier of drug-delivery payloads actively reaching more areas of the heart and arteries, allowing them novel therapeutic agents for CVDs. Herein, due to the limited availability of literature, we only focused on NPs mechanism in the cardiovascular system and various treatment-based approaches that opens a new window for future research and versatile approach in the field of medical and clinical applications. Moreover, current challenges and limitations for the detection of CVDs has also discussed.
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Doenças Cardiovasculares , Nanopartículas , Humanos , Nanomedicina/métodos , Medicina de Precisão , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/tratamento farmacológico , Nanopartículas/uso terapêutico , Diagnóstico por ImagemRESUMO
Gastric cancer (G.C) is one of the most lethal cancer types worldwide. Current treatment requires surgery along with chemotherapy, which causes obstacles for speedy recovery. The discovery of novel drugs is needed for better treatment of G.C with minimum side effects. Latcripin-7A (LP-7A) is a newly discovered peptide extracted from Lentinula edodes. It is recently studied for its anti-cancer activity. In this study, LP-7A was modeled using a phyre2 server. Anti-proliferation effects of LP-7A on G.C cells were examined via CCK-8, colony formation, and morphology assay. Apoptosis of LP-7A treated G.C cells was evaluated via Hoechst Stain, western blot and flow cytometry. Autophagy was assessed via acridine orange staining and western blot. The cell cycle was assessed via flow cytometry assay and western blot. Pathway was studied via western blot and STRING database. Anti-migratory effects of LP-7A treated G.C cells were analyzed via wound healing, western blot, and migration and invasion assay. LP-7A effectively inhibited the growth of G.C cells by inhibiting the PI3K/Akt/mTOR pathway. G.C cells treated with LP-7A arrested the cell cycle at the G1 phase, contributing to the inhibition of migration and invasion. Furthermore, LP-7A induced apoptosis and autophagy in gastric cancer cells. These results indicated that LP-7A is a promising anti-cancer agent. It affected the proliferation and growth of G.C cells (SGC-7901 and BGC-823) by inducing apoptosis, autophagy, and inhibiting cell cycle at the G1 phase in G.C cells.
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Fosfatidilinositol 3-Quinases , Autofagia/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-akt , Cogumelos Shiitake , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas , Serina-Treonina Quinases TORRESUMO
Latcripin-16 (Lp16-PSP) is a gene that was extracted as a result of de novo characterization of the Lentinula edodes strain C91-3 transcriptome. The aim of the present study was to clone, express, and investigate the selective in vitro anticancer potential of Lp16-PSP in human cell lines. Lp16-PSP was analyzed using bioinformatics tools, cloned in a prokaryotic expression vector pET32a (+) and transformed into E. coli Rosetta gami. It was expressed and solubilized under optimized conditions. The differential scanning fluorometry (DSF)-guided refolding method was used with modifications to identify the proper refolding conditions for the Lp16-PSP protein. To determine the selective anticancer potential of Lp16-PSP, a panel of human cancerous and non-cancerous cell lines was used. Lp16-PSP protein was identified as endoribonuclease L-PSP protein and a member of the highly conserved YjgF/YER057c/UK114 protein superfamily. Lp16-PSP was expressed under optimized conditions (37 °C for 4 h following induction with 0.5 mM isopropyl ß-D-1-thiogalactopyranoside). Solubilization was achieved with mild solubilization buffer containing 2 M urea using the freeze-thaw method. The DSF guided refolding method identified the proper refolding conditions (50 mM Tris-HCl, 100 mM NaCl, 1 mM EDTA, 400 mM Arginine, 0.2 mM GSH and 2 mM GSSG; pH 8.0) for Lp16-PSP, with a melting transition of ~ 58 °C. A final yield of ~ 16 mg of purified Lp16-PSP from 1 L of culture was obtained following dialysis and concentration by PEG 20,000. A Cell Counting Kit-8 assay revealed the selective cytotoxic effect of Lp16-PSP. The HL-60 cell line was demonstrated to be most sensitive to Lp16-PSP, with an IC50 value of 74.4 ± 1.07 µg/ml. The results of the present study suggest that Lp16-PSP may serve as a potential anticancer agent; however, further investigation is required to characterize this anticancer effect and to elucidate the molecular mechanism underlying the action of Lp16-PSP.
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Proteínas Fúngicas/genética , Proteínas Fúngicas/farmacologia , Proteínas Recombinantes/farmacologia , Cogumelos Shiitake/química , Cogumelos Shiitake/genética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/genética , Expressão Gênica , Humanos , Proteínas Recombinantes/genéticaRESUMO
Due to the high mortality rate and an increase in breast cancer incidence, it has been challenging for researchers to come across an effective chemotherapeutic strategy with minimum side effects. Therefore, the need for the development of effective chemotherapeutic drugs is still on the verge. Consequently, we approached a new mechanism to address this issue. The naturally available peptide named latcripin-7A (LP-7A), extracted from a mushroom called Lentinula edodes, provided us promising results in terms of growth arrest, apoptosis, and autophagy in breast cancer cells (MCF-7 and MDA-MB-231). Expressions of protein markers for apoptosis, autophagy, and cell cycle were confirmed via Western blot analysis. Migration and invasion assays were performed to analyze the anti-migratory and anti-invasive properties of LP-7A, while cell cycle analysis was performed via flow cytometry to evaluate its affect over cell growth. Supportive assays were performed like acridine orange, Hoechst 33258 stain, DNA fragmentation, and mitochondrial membrane potential (MMP) to further confirm the anticancer effect of LP-7A on breast cancer cell lines. It is concluded that LP-7A effectively reduces migration and promotes apoptosis as well as autophagy in MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell growth arrest at G0/G1 phase and decreasing mitochondrial membrane potential without adverse effects on MCF-10A normal breast cells. KEY POINTS: ⢠In this study, we have investigated the anti-cancer activity of novel latcripin-7A (LP-7A), a protein extracted as a result of de novo characterization of Lentinula edodes C91-3. ⢠We conclude in our research work that LP-7A can initiate diverse cell death-related events, i.e., apoptosis and autophagy in both triple-positive and triple-negative breast cancer cell lines by interacting with different nodes of cellular signaling that can further be investigated in vivo to gain a better understanding.
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Neoplasias da Mama , Cogumelos Shiitake , Apoptose , Autofagia , Neoplasias da Mama/tratamento farmacológico , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , PeptídeosRESUMO
Various dietary fibers are considered to prevent obesity by modulating the gut microbiota. Cordyceps sinensis polysaccharide (CSP) is a soluble dietary fiber known to have protective effects against obesity and related diseases, but whether these effects induce any side effects remains unknown. The function and safety of CSP were tested in high-fat diet (HFD)-feding C57BL/6J mice. The results revealed that even though CSP supplementation could prevent an increase in body weight, it aggravated liver fibrosis and steatosis as evidenced by increased inflammation, lipid metabolism markers, insulin resistance (IR) and alanine aminotransferase (ALT) in HFD-induced obesity. 16S rDNA gene sequencing was used to analyze the gut microbiota composition, and the relative abundance of the Actinobacteria phylum, including the Olsenella genus, was significantly higher in CSP-treated mice than in HFD-fed mice. CSP supplementation may increase the proportion of Actinobacteria, which can degrade CSP. The high level of Actinobacteria aggravated the disorder of the intestinal flora and contributed to the progression from obesity to nonalcoholic steatohepatitis (NASH) and related diseases.
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Cordyceps , Dieta Hiperlipídica/efeitos adversos , Fibras na Dieta/administração & dosagem , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica/metabolismo , Polissacarídeos/administração & dosagem , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Peso Corporal , Cordyceps/metabolismo , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/metabolismo , Resistência à Insulina , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia , Polissacarídeos/isolamento & purificaçãoRESUMO
BACKGROUND: Obesity is a severe public health threat worldwide. Emerging evidence suggests that gut microbiota dysbiosis is closely associated with obesity and its related metabolic complications. The aim of the present study is to investigate the effects of polysaccharide extracted from WuGuChong (PEW) on high-fat diet (HFD)-induced obesity, and the potential mechanisms involving modulation of the gut microbiota composition. METHODS: Mice were fed a normal chow diet and a high-fat diet with or without PEW (300 mg/kg/day) by oral gavage for 8 weeks. Body weight, obesity-related metabolic disorders, and gut microbiota were examined at the end of the experiment. RESULTS: PEW supplementation reduces body weight, adipose hypertrophy, liver steatosis, insulin resistance and systemic inflammation in HFD-fed mice, as well as maintains intestinal epithelium integrity. High-throughput 16S rRNA analysis demonstrates that PEW supplementation alters the composition of gut microbiota. The Firmicutes to Bacteroidetes ratio and the relative abundance of Proteobacteria are increased in HFD-fed mice, which are reversed by PEW supplementation to approximately the control levels. CONCLUSIONS: Our results suggest that PEW may be used as a bioactive ingredient to prevent obesity and its related metabolic disorders by modulating the composition of gut microbiota.
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Present study aimed to elucidate the anticancer effect and the possible molecular mechanism underlying the action of Latcripin 1 (LP1), from the mushroom Lentinula edodes strain C91-3 against gastric cancer cell lines SGC-7901 and BGC-823. Cell viability was measured by Cell Counting Kit-8 (CCK-8); morphological changes were observed by phase contrast microscope; autophagy was determined by transmission electron microscope and fluorescence microscope. Apoptosis and cell cycle were assessed by flow cytometer; wound-healing, transwell migration and invasion assays were performed to investigate the effect of LP1 on gastric cancer cell's migration and invasion. Herein, we found that LP1 resulted in the induction of autophagy by the formation of autophagosomes and conversion of light chain 3 (LC3I into LC3II. LP1 up-regulated the expression level of autophagy-related gene (Atg7, Atg5, Atg12, Atg14) and Beclin1; increased and decreased the expression level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins respectively, along with the activation of Caspase-3. At lower-doses, LP1 have shown to arrest cells in the S phase of the cell cycle and decreased the expression level of matrix metalloproteinase MMP-2 and MMP-9. In addition, it has also been shown to regulate the phosphorylation of one of the most hampered gastric cancer pathway, that is, protein kinase B/mammalian target of rapamycin (Akt/mTOR) channel and resulted in cell death. These findings suggested LP1 as a potential natural anti-cancer agent, for exploring the gastric cancer therapies and as a contender for further in vitro and in vivo investigations.
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Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteínas Fúngicas/farmacologia , Cogumelos Shiitake/química , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fase S/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
The aim of this study is to assess the antibacterial and anti-biofilm properties of the lipid extract from Mantidis ootheca against the gentamycin resistant Pseudomonas aeruginosa. The chemical composition of the lipid extract and its relative proportion were determined using the technique of gas chromatography coupled with mass spectrometry (GC-MS). Antibacterial susceptibility tests were performed using a disc diffusion assay and the minimum inhibition concentration (MIC) was determined by way of the agar dilution method. The anti-biofilm test was carried out with crystal violet staining and scanning electron microscopy (SEM). There were 16 compounds detected, and the most abundant components were sesquiterpenoids, monoterpenes, and trace aromatic compounds. The MIC for P. aeruginosa was 4 mg/ml and the eradication effect on preformed biofilms was established and compared with a ciprofloxacin control. The results of our study indicated that a lipid extract from M. ootheca could be used as a topical and antibacterial agent with anti-biofilm activity in the future.
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Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Mantódeos , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Cromatografia Gasosa-Espectrometria de Massas , Mantódeos/química , Testes de Sensibilidade MicrobianaRESUMO
Malignant ascites is a highly severe and intractable complication of advanced or recurrent malignant tumors that is often immunotherapy-resistant. Rhizoma Pleionis is widely used in traditional medicine as an antimicrobial and anticancer agent, but its effectiveness in treating malignant ascites is unclear. In the current study, we investigated the effect of polysaccharides isolated from Rhizoma Pleionis (PRP) on murine hepatocarcinoma H22 cells in an ascites model. We have found that the main components of PRP, that presented a relative molecular weight of 383.57 kDa, were mannose and glucose. We also found that PRP reduced the occurrence of abdominal ascites and increased survival in our mouse model. An immune response in the ascites tumor model was observed by performing a lymphocytes proliferation experiment and an E-rosette test. The ratios of CD8+ cytotoxic T cells and NK cells in the spleen were examined by flow cytometry, and the mRNA expression of Foxp3+in CD4âºCD25⺠(T regulatory Tregs) was measured by RT-PCR (reverse transcription-polymerase chain reaction). The levels of the cytokines TNF-α (tumor necrosis factor), VEGF (vascular endothelial growth factor), IL-2 (interleukin), and IFN-γ (interferon) in the serum and ascites supernatants were measured by ELISA. The expression of Foxp3 and Stat3 in peritoneal cells in the mouse model was measured by immunocytochemistry. The results indicated that PRP increased H22 tumor cell apoptosis in vivo by activating and enhancing the immune response. Furthermore, the effects of PRP on the proliferation of H22 cells were assessed by the CCK8 assay, Hoechest 33258, and TUNEL staining in vitro. We found that PRP suppressed the proliferation of H22 tumor cells but had no effect on BRL (Big rat liver) -3A rat hepatoma normal cells in vitro. Next, we investigated the underlying immunological mechanism by which PRP inhibits malignant ascites. PRP induced tumor cell apoptosis by inhibiting the Jak1â»Stat3 pathway and by activating Caspase-3 and Caspase-8 to increase the Bax/Bcl-2 ratio. Collectively, our results indicate that PRP exhibits significant antitumor properties in H22 cells in vivo and in vitro, indicating that PRP may be used as a new therapeutic drug for cancer treatment.
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Antineoplásicos Fitogênicos/uso terapêutico , Ascite/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Orchidaceae/química , Polissacarídeos/uso terapêutico , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Ascite/patologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/química , Rizoma/químicaRESUMO
Microorganisms provide both beneficial and harmful effects to human beings. Beneficial effects come from the symbiotic relationship that exists between humans and microbiota, but then several human illnesses have turned some friendly microbes into opportunistic pathogens, causing several microbial-related diseases. Various efforts have been made to create and utilize antimicrobial agents in the treatment and prevention of these infections, but such efforts have been hampered by the emergence of antimicrobial resistance. Despite extensive studies on drug discovery to alleviate this problem, issues with the toxicity and tolerance of certain compounds and continuous microbial evolution have forced researchers to focus on screening various phytochemical dietary compounds for antimicrobial activity. Linolenic acid and its derivatives (eicosapentaenoic acid and docosahexaenoic acid) are omega-3 fatty acids that have been studied due to their role in human health, being important for the brain, the eye, the cardiovascular system, and general human growth. However, their utilization as antimicrobial agents has not been widely appreciated, perhaps due to a lack of understanding of antimicrobial mechanisms, toxicity, and route of administration. Therefore, this review focuses on the efficacy, mechanism, and toxicity of omega-3 fatty acids as alternative therapeutic agents for treating and preventing diseases associated with pathogenic microorganisms.
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Anti-Infecciosos/química , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Ácidos Graxos Ômega-3/química , Animais , Animais Geneticamente Modificados , Antioxidantes/química , Membrana Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Ácidos Docosa-Hexaenoicos/química , Farmacorresistência Bacteriana , Ácido Eicosapentaenoico/química , Peixes , Humanos , Lipídeos/química , Camundongos , Microbiota , Ratos , Ácido alfa-Linolênico/químicaRESUMO
In recent decades, bacteria's therapeutic role has aroused attention in medicinal and pharmaceutical research. While bacteria are considered among the primary agents for causing cancer, recent research has shown intriguing results suggesting that bacteria can be effective agents for cancer treatment - they are the perfect vessels for targeted cancer therapy. Several bacterial strains/species have been discovered to possess inherent oncolytic potentials to invade and colonize solid tumors in vivo. The therapeutic strategy of using bacteria for treating cancer is considered to be effective; however, the severe side effects encountered during the treatment resulted in the abandonment of the therapy. State-of-the-art genetic engineering has been recently applied to bacteria therapy and resulted in a greater efficacy with minimum side effects. In addition, the anti-cancer potential of tumor-targeting bacteria through oral administration circumvents the use of the intravenous route and the associated adverse effects. This review aims to provide a comprehensive summary of the latest literature on the role of bacteria in cancer treatment.
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The formation of inclusion bodies (IBs) is considered as an Achilles heel of heterologous protein expression in bacterial hosts. Wide array of techniques has been developed to recover biochemically challenging proteins from IBs. However, acquiring the active state even from the same protein family was found to be an independent of single established method. Here, we present a new strategy for the recovery of wide sub-classes of recombinant protein from harsh IBs. We found that numerous methods and their combinations for reducing IB formation and producing soluble proteins were not effective, if the inclusion bodies were harsh in nature. On the other hand, different practices with mild solubilization buffers were able to solubilize IBs completely, yet the recovery of active protein requires large screening of refolding buffers. With the integration of previously reported mild solubilization techniques, we proposed an improved method, which comprised low sarkosyl concentration, ranging from 0.05 to 0.1% coupled with slow freezing (- 1 °C/min) and fast thaw (room temperature), resulting in greater solubility and the integrity of solubilized protein. Dilution method was employed with single buffer to restore activity for every sub-class of recombinant protein. Results showed that the recovered protein's activity was significantly higher compared with traditional solubilization/refolding approach. Solubilization of IBs by the described method was proved milder in nature, which restored native-like conformation of proteins within IBs.
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Fracionamento Químico/métodos , Escherichia coli/química , Corpos de Inclusão/química , Proteínas Recombinantes/isolamento & purificação , Escherichia coli/genética , Escherichia coli/metabolismo , Corpos de Inclusão/genética , Corpos de Inclusão/metabolismo , Dobramento de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Cogumelos Shiitake/genética , SolubilidadeRESUMO
The recombinant protein of Latcripin-4 regulator of chromosome condensation 1 (RCC1) and ankyrin (ANK) domains were expressed and the antitumor activity of Latcripin-4 on HepG2 cells was studied. First, the Latcripin-4 transcript was selected from the medicinal mushroom Lentinus edodes C91-3 transcriptome by bioinformatics. Then the full-length gene of Latcripin-4 was isolated with 3'-full rapid amplification of cDNA ends (RACE) and 5'-full RACE methods according to the transcriptome. The RCC1 and ANK domains from the full-length gene were selected and inserted into the expression vector pET-32a (+) and expressed in Escherichia coli Rosetta-gami (DE3). Western blotting indicated that the protein was expressed successfully. The biological function of Latcripin-4 RCC1 and ANK domain protein on HepG2 cells was studied with the CCK-8 assay. All results demonstrated that Latcripin-4 RCC1 and ANK domain protein can inhibit the growth of human HepG2 liver cancer cells, which brings new insights to identifying antitumor proteins from medicinal food for cancer therapy.
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Antineoplásicos Fitogênicos/farmacologia , Proteínas Fúngicas/química , Proteínas Fúngicas/farmacologia , Expressão Gênica , Cogumelos Shiitake/química , Antineoplásicos Fitogênicos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Células Hep G2 , Humanos , Domínios Proteicos , Cogumelos Shiitake/genética , Cogumelos Shiitake/metabolismoRESUMO
Lentinula edodes C91-3 is an edible mushroom that has demonstrated a remarkable anti-tumor effect in various cancer cells both in vitro and in vivo. In the present study, we report the ability of recombinant thioredoxin-like latcripin 11 (LP-11) of Lentinula edodes C91-3 to suppress the proliferation of various cancer cells. The LP-11 gene of Lentinula edodes C91-3 was cloned in the pET-32a(+) expression vector and expressed in a prokaryotic system. The expressed protein was refolded by gradual dialysis and purified by affinity gel filtration chromatography. The antioxidant activity of LP-11 was tested by 1,1-dipheny l-2-picrylhydrazyl (DPPH) assay. The anti-tumor activity of recombinant LP-11 was tested in eight kinds of tumor cell lines by CCK-8 assay. Recombinant LP-11 significantly suppressed the proliferation of various cancer cells, but not normal human umbilical vein endothelial cells. Human lymphoma U937 cells exhibited the most sensitivity to LP-11 protein. U937 cell apoptosis was assessed by Annexin V staining coupled with flow cytometry, and mitochondrial morphology was analyzed by light and electron microscopy. It was revealed that recombinant LP-11 induced apoptosis in human leukemic monocyte lymphoma U937 cells. Our findings suggest that recombinant LP-11 is a promising agent for the treatment of lymphoma.
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Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Proteínas Fúngicas/farmacologia , Neoplasias/metabolismo , Proteínas Recombinantes/farmacologia , Cogumelos Shiitake/metabolismo , Células A549 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas Fúngicas/genética , Células HL-60 , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Células K562 , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Células U937RESUMO
Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity. Many researchers, including our own group, are focusing on the anticancer potential of different mushrooms and the underlying molecular mechanism behind their action. The aim of this review is to discuss PI3K/AKT, Wnt-CTNNB1, and NF-κB signaling pathways, the occurrence of genetic alterations in them, the association of these aberrations with different human cancers and how different nodes of these pathways are targeted by various substances of mushroom origin. We have given evidence to propose the therapeutic attributes and possible mode of molecular actions of various mushroom-originated compounds. However, anticancer effects were typically demonstrated in in vitro and in vivo models and very limited number of studies have been conducted in the human population. It is our belief that this review will help the research community in designing concrete preclinical and clinical studies to test the anticancer potential of mushroom-originated compounds on different cancers harboring particular genetic alteration(s).
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Agaricales/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Transdução de Sinais/efeitos dos fármacosRESUMO
Pseudomonas aeruginosa is a ubiquitous Gram negative opportunistic pathogen capable of causing severe nosocomial infections in humans, and tobramycin is currently used to treat P. aeruginosa associated lung infections. Quorum sensing regulates biofilm formation which allows the bacterium to result in fatal infections forcing clinicians to extensively use antibiotics to manage its infections leading to emerging multiple drug resistant strains. As a result, tobramycin is also becoming resistant. Despite extensive studies on drug discovery to alleviate microbial drug resistance, the continued microbial evolution has forced researchers to focus on screening various phytochemicals and dietary compounds for antimicrobial potential. Linolenic acid (LNA) is an essential fatty acid that possesses antimicrobial actions on various microorganisms. It was hypothesized that LNA may affect the formation of biofilm on P. aeruginosa and improve the potency of tobramycin. The present study demonstrated that LNA interfered with cell-to-cell communication and reduced virulence factor production. It further enhanced the potency of tobramycin and synergistically inhibited biofilm formation through P. aeruginosa quorum sensing systems. Therefore, LNA may be considered as a potential agent for adjunctive therapy and its utilization may decrease tobramycin concentration in combined treatment thereby reducing aminoglycoside adverse effects.
RESUMO
Candida albicans is a minor component of the oral microbiota and an opportunistic pathogen that takes advantage of the immunocompromised host and causes oral mucositis and oral candidiasis. This organism is able to undergo phenotypic modification from a yeast to hyphae growth phase, one of the key arsenals for immune cell evasion, tissue invasion and biofilm formation. The latter property coupled with overgrowth and immune compromising factors such as HIV/AIDS, cancer treatments, organ transplantation, diabetes, corticosteroid use, dentures, and broad-spectrum antibiotic use have modified the fungus from a normal component of the microflora to a foe of an oral cavity and resulting in reduced sensitivity towards commonly utilised antifungal agents. Hence, the need for alternative therapy to curb this plight is of importance. Making use of biomolecules produced by Streptococcus mutans, application of lactoferrin which is a nonspecific host defense factor found in saliva with metal chelating and broader antimicrobial properties, use of probiotics which have the capacity to boost the host immunity through eliciting Immunoglobulin A synthesis, and perturbing the pathogen's environment via competition of space and food, and application of photodynamic therapy can help to manage the burden of oral candidiasis.