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1.
Int J Mol Sci ; 25(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38892254

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Known as COVID-19, it has affected billions of people worldwide, claiming millions of lives and posing a continuing threat to humanity. This is considered one of the most extensive pandemics ever recorded in human history, causing significant losses to both life and economies globally. However, the available evidence is currently insufficient to establish the effectiveness and safety of antiviral drugs or vaccines. The entry of the virus into host cells involves binding to angiotensin-converting enzyme 2 (ACE2), a cell surface receptor, via its spike protein. Meanwhile, transmembrane protease serine 2 (TMPRSS2), a host surface protease, cleaves and activates the virus's S protein, thus promoting viral infection. Plant protease inhibitors play a crucial role in protecting plants against insects and/or microorganisms. The major storage proteins in sweet potato roots include sweet potato trypsin inhibitor (SWTI), which accounts for approximately 60% of the total water-soluble protein and has been found to possess a variety of health-promoting properties, including antioxidant, anti-inflammatory, ACE-inhibitory, and anticancer functions. Our study found that SWTI caused a significant reduction in the expression of the ACE2 and TMPRSS2 proteins, without any adverse effects on cells. Therefore, our findings suggest that the ACE2 and TMPRSS2 axis can be targeted via SWTI to potentially inhibit SARS-CoV-2 infection.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Antivirales , Ipomoea batatas , SARS-CoV-2 , Serina Endopeptidasas , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Humanos , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/metabolismo , Animales , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Ipomoea batatas/virología , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , COVID-19/virología , COVID-19/metabolismo , Inhibidores de Tripsina/farmacología , Inhibidores de Tripsina/metabolismo , Internalización del Virus/efectos de los fármacos , Chlorocebus aethiops , Células Vero , Regulación hacia Abajo/efectos de los fármacos , Ratones
2.
Int J Mol Sci ; 24(20)2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37894745

RESUMEN

Coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. This highly contagious pneumonia remains a significant ongoing threat. Uncertainties persist about the virus's effects on human health, underscoring the need for treatments and prevention. Current research highlights angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key targets against SARS-CoV-2. The virus relies on ACE2 to enter cells and TMPRSS2 to activate its spike protein. Inhibiting ACE2 and TMPRSS2 expression can help prevent and treat SARS-CoV-2 infections. Anisomeles indica (L.) Kuntze, a medicinal plant in traditional Chinese medicine, shows various promising pharmacological properties. In this study, ethanolic extracts of A. indica were examined both in vivo (250 and 500 µM) and in vitro (500 µM). Through Western blotting analysis, a significant reduction in the expression levels of ACE2 and TMPRSS2 proteins was observed in HepG2 (human hepatocellular carcinoma) cells and HEK 293T (human embryonic kidney) cell lines without inducing cellular damage. The principal constituents of A. indica, namely, ovatodiolide (5 and 10 µM), anisomlic acid (5 and 10 µM), and apigenin (12.5 and 25 µM), were also found to produce the same effect. Furthermore, immunohistochemical analysis of mouse liver, kidney, and lung tissues demonstrated a decrease in ACE2 and TMPRSS2 protein expression levels. Consequently, this article suggests that A. indica and its constituents have the potential to reduce ACE2 and TMPRSS2 protein expression levels, thus aiding in the prevention of SARS-CoV-2 infections.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Animales , Ratones , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , SARS-CoV-2/metabolismo , Pulmón/metabolismo , Procesamiento Proteico-Postraduccional , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo
3.
Int J Mol Sci ; 24(11)2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37298398

RESUMEN

One of the most popular edible mushrooms in the world, Flammulina velutipes, has been shown to possess pharmacological properties such as anti-inflammatory and antioxidant properties. However, the potential activity of the brown strain of F. velutipes, a hybrid between the white and yellow strains, has not been thoroughly investigated. Numerous studies have been conducted in recent years to determine whether natural products can aid in improving or treating kidney diseases. In this study, we focused on the renoprotective effects of the brown strain of F. velutipes on cisplatin-induced acute kidney injury (AKI) in mice. Mice were pretreated with water extract from the brown strain of F. velutipes (WFV) from day 1 to day 10, with a single-dose intraperitoneal injection of cisplatin on day 7 to induce AKI. Our results demonstrated that WFV administration resulted in a reduction in weight loss and the amelioration of renal function and renal histological changes in mice with cisplatin-induced AKI. WFV improved antioxidative stress and anti-inflammatory capacity by increasing antioxidant enzymes and decreasing inflammatory factors. The expression of related proteins was determined via Western blot analysis, which showed that WFV could improve the expression of apoptosis and autophagy. We used the PI3K inhibitor Wortmannin and found that WFV achieved a protective effect by modulating the PI3K/AKT pathway and the expression of autophagy. Overall, WFV as a natural substance could be used as a new therapeutic agent for AKI.


Asunto(s)
Lesión Renal Aguda , Flammulina , Ratones , Animales , Antioxidantes/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Cisplatino/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Estrés Oxidativo , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Autofagia
4.
Cancer Sci ; 113(8): 2862-2877, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35633182

RESUMEN

Several epidemiological studies have suggested that Epstein-Barr virus (EBV) lytic infection is essential for the development of nasopharyngeal carcinoma (NPC), as the elevation of antibody titers against EBV lytic proteins is a common feature of NPC. Although ZEBRA protein is a key trigger for the initiation of lytic infection, whether its expression affects the prognosis and pathogenesis of NPC remains unclear. In this study, 64 NPC biopsy specimens were analyzed using immunohistochemistry. We found that ZEBRA was significantly associated with a worsening of progression-free survival in NPC (adjusted hazard ratio, 3.58; 95% confidence interval, 1.08-11.87; p = 0.037). Moreover, ZEBRA expression positively correlated with key endocrinological proteins, estrogen receptor α, and aromatase. The transcriptional level of ZEBRA is activated by estrogen in an estrogen receptor α-dependent manner, resulting in an increase in structural gene expression levels and extracellular virus DNA copy number in NPC cell lines, reminiscent of lytic infection. Interestingly, it did not suppress cellular proliferation or increase apoptosis, in contrast with cells treated with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate, indicating that viral production induced by estrogen is not a cell lytic phenomenon. Our results suggest that intratumoral estrogen overproduced by aromatase could induce ZEBRA expression and EBV reactivation, contributing to the progression of NPC.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Transactivadores , Aromatasa , Receptor alfa de Estrógeno , Estrógenos , Herpesvirus Humano 4/patogenicidad , Humanos , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/virología , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Transactivadores/genética
5.
Int J Mol Sci ; 23(23)2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36499094

RESUMEN

The current global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of COVID-19 has infected hundreds of millions of people, killed millions, and continues to pose a threat. It has become one of the largest epidemics in human history, causing enormous damage to people's lives and economies in the whole world. However, there are still many uncertainties and continued attention to the impact of SARS-CoV-2 on human health. The entry of SARS-CoV-2 into host cells is facilitated by the binding of the spike protein on the virus surface to the cell surface receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, transmembrane protease serine 2 (TMPRSS2) is a host surface protease that cleaves and proteolytically activates its S protein, which is necessary for viral infection. Thus, SARS-CoV-2 uses the ACE2 receptor for cell entry and initiates the S protein using the protease TMPRSS2. Schizophyllum commune (SC) is one of the most widely distributed fungi, often found on the rotten wood of trees that has been found to have various health benefits, including anticancer, antimicrobial activity, antiparasitic, and immunomodulatory function. In this article, SC significantly diminished the expression ACE2 and TMPRSS2 protein in vitro and in vivo without cell damage. In addition, adenosine from SC was also proven in this experiment to reduce the ACE2 and TMPRSS2 expression. Thus, our findings suggest that SC and adenosine exhibit potential for the repression of SARS-CoV-2 infection via the ACE2 and TMPRSS2 axis.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Productos Biológicos , COVID-19 , Schizophyllum , Serina Endopeptidasas , Humanos , Adenosina , Enzima Convertidora de Angiotensina 2/genética , SARS-CoV-2/metabolismo , Schizophyllum/química , Serina Endopeptidasas/genética , Productos Biológicos/farmacología
6.
Molecules ; 27(16)2022 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-36014558

RESUMEN

Antrodia camphorata is an endemic mushroom in Taiwan. This study was designed to screen anti-inflammatory compounds from the methanolic extract of the mycelium of A. camphorata on nitric oxide (NO) production in RAW 264.7 cells induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA (dsRNA) known to be present in viral infection. A combination of bioactivity-guided isolation with an NMR-based identification led to the isolation of 4-acetylantroquinonol B (1), along with seven compounds. The structure of new compounds (4 and 5) was elucidated by spectroscopic experiments, including MS, IR, and NMR analysis. The anti-inflammatory activity of all isolated compounds was assessed at non-cytotoxic concentrations. 4-Acetylantroquinonol B (1) was the most potent compound against poly I:C-induced NO production in RAW 264.7 cells with an IC50 value of 0.57 ± 0.06 µM.


Asunto(s)
Antrodia , Animales , Antiinflamatorios/química , Antrodia/química , Ratones , Óxido Nítrico , Poli I-C/farmacología , Polyporales , Células RAW 264.7
7.
Bioorg Chem ; 104: 104333, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33142408

RESUMEN

A new method was developed for synthesis of 1,2,4-triazole-3-carboxylates 5a-p and 6 from nitrilimines 3a-p through amination and heterocyclization two-steps reactions. All of 1,2,4-triazole-3-carboxylates 5 and 6 were characterized by spectroscopy technique. Based on the SAR study of anti-inflammation activity, most of these compounds showed potential anti-inflammatory activity on NO inhibition in LPS-induced RAW 264.7 cells (IC50 < 7.0 µM) compared with Celecoxib and Indomethacin. Several potential compounds 5b-h, 5j, 5l, 5n, and 5o were subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. Compound 5d showed extraordinary COX-2 inhibition (IC50 = 17.9 nM) and the best selectivity (COX-1/COX-2 = 1080). Furthermore, 5 mg/kg compound 5d exhibited better in vivo anti-inflammation and gastric protection results compared to 10 mg/kg Indomethacin. Docking experiments of 5d into COX-2 binding pocket have been evaluated. Following the bioactivities experimental data, the potential drug candidate 5d, significantly exhibited better anti-inflammatory effect than Indomethacin.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Ácidos Carboxílicos/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Triazoles/farmacología , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/química , Carragenina , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/química , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Edema/metabolismo , Edema/patología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Modelos Moleculares , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Proteínas Recombinantes/metabolismo , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/química
8.
J Nat Prod ; 81(5): 1143-1147, 2018 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-29676580

RESUMEN

12- epi-Lycopodine (1), a Lycopodium alkaloid, along with lycopodine (2) and huperzine A (3), were discovered in the mycelium of Paraboeremia sp. Lsl3KI076, a UV-irradiated strain of Paraboeremia sp. Lsl3, an endophytic fungus from Lycopodium serratum Thunb. var. longipetiolatum Spring. Additionally, a trace of 1 was isolated from Phlegmariurus nummulariifolius (Blume) Ching, and the structure was elucidated on the basis of spectroscopic data. This is the first report proving that a new naturally occurring Lycopodium alkaloid can be obtained from an endophytic fungus.


Asunto(s)
Alcaloides/química , Hongos/química , Lycopodium/química , Quinolizinas/química , Sesquiterpenos/química , Rayos Ultravioleta
9.
Molecules ; 22(5)2017 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-28524081

RESUMEN

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1ß, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation.


Asunto(s)
Acetaminofén/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Eriobotrya/química , Sustancias Protectoras/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Triterpenos/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Catalasa/genética , Catalasa/metabolismo , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colesterol/sangre , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Inyecciones Intraperitoneales , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Hígado/efectos de los fármacos , Masculino , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Sustancias Protectoras/aislamiento & purificación , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Triglicéridos/sangre , Triterpenos/aislamiento & purificación , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
10.
Bioorg Med Chem Lett ; 26(11): 2636-40, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27086123

RESUMEN

Three new Lycopodium alkaloids, serralongamines B-D (1-3), have been isolated from the club moss Lycopodium serratum var. longipetiolatum, and the structures were elucidated on the basis of spectroscopic data and chemical transformation. 1 and 3 significantly exhibited the inhibitory activity against foam cell formation in human macrophages, one of characteristic features of early atherosclerotic lesions.


Asunto(s)
Células Espumosas/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Lycopodium/química , Macrófagos/efectos de los fármacos , Quinolinas/farmacología , Relación Dosis-Respuesta a Droga , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Humanos , Estructura Molecular , Quinolinas/química , Quinolinas/aislamiento & purificación , Relación Estructura-Actividad
11.
Biochim Biophys Acta ; 1840(6): 2060-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24582939

RESUMEN

BACKGROUND: Transplanted mesenchymal stem cells (MSC) can differentiate into cardiac cells that have the potential to contribute to heart repair following ischemic injury. Overexpression of GATA-4 can significantly increase differentiation of MSC into cardiomyocytes (CM). However, the specific impact of GATA-4 overexpression on the electrophysiological properties of MSC-derived CM has not been well documented. METHODS: Adult rat bone marrow MSC were retrovirally transduced with GATA-4 (MSC(GATA-4)) and GFP (MSC(Null)) and subsequently co-cultured with neonatal rat ventricular cardiomyocytes (CM). Electrophysiological properties and mRNA levels of ion channels were assessed in MSC using patch-clamp technology and real-time PCR. RESULTS: MSC(GATA-4) exhibited higher levels of the TTX-sensitive Na(+) current (INa.TTX), L-type calcium current (ICa.L), transient outward K(+) current (Ito), delayed rectifier K(+) current (IKDR) and inwardly rectifying K(+) current (IK1) channel activities reflective of electrophysiological characteristics of CM. Real-time PCR analyses showed that MSC(GATA-4) exhibited upregulated mRNA levels of Kv1.2, Kv2.1, SCN2a1, CCHL2a, KV1.4 and Kir1.1 channels versus MSC(Null). Interestingly, MSC(GATA-4) treated with IGF-1 neutralizing antibodies resulted in a significant decrease in Kir1.1, Kv2.1, KV1.4, CCHL2a and SCN2a1 channel mRNA expression. Similarly, MSC(GATA-4) treated with VEGF neutralizing antibodies also resulted in an attenuated expression of Kv2.1, Kv1.2, Kv1.4, Kir1.1, CCHL2a and SCN2a1 channel mRNAs. CONCLUSIONS: GATA-4 overexpression increases Ito, IKDR, IK1, INa.TTX and ICa.L currents in MSC. Cytokine (VGEF and IGF-1) release from GATA-4 overexpressing MSC can partially account for the upregulated ion channel mRNA expression. GENERAL SIGNIFICANCE: Our results highlight the ability of GATA4 to boost the cardiac electrophysiological potential of MSC.


Asunto(s)
Factor de Transcripción GATA4/fisiología , Células Madre Mesenquimatosas/fisiología , Animales , Células Cultivadas , Citocinas/fisiología , Factor 2 de Crecimiento de Fibroblastos/fisiología , Factor I del Crecimiento Similar a la Insulina/fisiología , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/fisiología
12.
Int Heart J ; 56(5): 511-5, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26370375

RESUMEN

To investigate the relationship between KCNN3 SNP (single-nucleotide polymorphism) rs13376333 and risk of atrial fibrillation (AF) and to provide evidence for prevention and treatment for AF.The PubMed, Embase, OVID, Cochrane library, CNKI, and Wan Fang databases were searched to identify studies on the relationship between KCNN3 SNP rs13376333 polymorphism and atrial fibrillation. Two authors performed independent article reviews and study quality assessment using the Newcastle-Ottawa Scale (NOS) checklist.Seven studies involving 24,339 individuals were included in the meta-analysis. The overall combined OR of rs13376333 polymorphism was observed for both lone AF (OR: 1.58 [95%CI: 1.37 to 1.82]; P < 0.001; I(2) = 47.0%) and total AF (OR: 1.33 [95%CI: 1.14 to 1.54]; P < 0.001; I(2) = 0). Further, when stratified by ethnicity, control sources, sample sizes, and genotyping method, similar results were observed in both subgroups. Sensitivity analysis revealed that the source of control was the source of the heterogeneity for lone AF. Omission of any single study had little effect on the combined risk estimate. No evidence of publication bias was found.This meta-analysis suggests that KCNN3 SNP rs13376333 polymorphism significantly increases the risk of lone AF and total AF, which suggests the rs13376333 polymorphism of the KCNN3 gene may play an important role in the pathogenesis of AF.


Asunto(s)
Fibrilación Atrial/genética , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple
13.
Heliyon ; 10(13): e33414, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39035483

RESUMEN

Female Culter alburnus was faster in growth rate than males. In this study, the gynogenetic G2 and the pseudo-male G2' were used as the female and male parents, respectively, to breed a new national variety "All-female No.1" C. alburnus (AFC). Hormone induction, embryonic development, gonadal differentiation, and growth of AFC were studied. The results showed induction with low concentrations of 17α-methyltestosterone in a indoor-net cage culture was not effective. Under the stimulation of 17α-methyltestosterone, some gonads had a tendency to transform into testis, but not completely. There were three types of gonads in 5-month-old and four types of gonads in 12-month-old fishes, however, they all differentiated into ovaries in 15-month-old fishes. Testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction had a good effect resulting in ①a functional pseudo-male with normal testis development that could successfully extrude semen during the breeding period, ②a pseudo-male with normal testis development, but could not extrude semen, and ③the appearance of intersexual glands. The second experiment revealed that with common fish, all-female fish embryo had normal embryonic development. The development time and morphological characteristics of each stage were similar, but the development of the all-female embryo was slightly slower than the common embryos. The gonad differentiation of the all-female embryo were normal and none differentiated into testis, which indicated that all-female could ensure the female sex without affecting the normal gonad differentiation. The correlation between body weight, length, and month-age of all-female and common fish was strong. The all-female had faster growth rate and more uniform growth specification than the common fish. Therefore, the use of testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction could avoid complete degeneration of gonads into ovaries. The all-female embryo had the advantages of normal embryonic development and gonadal differentiation, faster growth, and uniform growth specification.

14.
Biomed Pharmacother ; 165: 115080, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37392658

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial pneumonia characterized by chronic and progressive fibrosis with an unknown etiology. Previous pharmacological studies have shown that Sanghuangporus sanghuang possesses various beneficial properties including immunomodulatory, hepatoprotective, antitumor, antidiabetic, anti-inflammatory, and neuroprotective effects. This study used a bleomycin (BLM)-induced IPF mouse model to illustrate the possible benefits of SS in ameliorating IPF. BLM was administered on day 1 to establish a pulmonary fibrosis mouse model, and SS was administered through oral gavage for 21 d. Hematoxylin and eosin (H&E) and Masson's trichrome staining results showed that SS significantly reduced tissue damage and decreased fibrosis expression. We observed that SS treatment resulted in a substantial lowering in the level of pro-inflammatory cytokines like TGF-ß, TNF-α, IL-1ß, and IL-6 as well as MPO. In addition, we observed a notable increase in glutathione (GSH) levels. Western blot analysis of SS showed that it reduces inflammatory factors (TWEAK, iNOS, and COX-2), MAPK (JNK, p-ERK, and p-38), fibrosis-related molecules (TGF-ß, SMAD3, fibronectin, collagen, α-SMA, MMP2, and MMP9), apoptosis (p53, p21, and Bax), and autophagy (Beclin-1, LC3A/B-I/II, and p62), and notably increases caspase 3, Bcl-2, and antioxidant (Catalase, GPx3, and SOD-1) levels. SS alleviates IPF by regulating the TLR4/NF-κB/MAPK, Keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-ß/SMAD3 pathways. These results suggest that SS has a pharmacological activity that protects the lungs and has the potential to improve pulmonary fibrosis.


Asunto(s)
FN-kappa B , Fibrosis Pulmonar , Ratones , Animales , FN-kappa B/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Receptor Toll-Like 4/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Sirtuina 1/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Pulmón , Fibrosis , Factor de Crecimiento Transformador beta/metabolismo , Apoptosis , Bleomicina/farmacología , Modelos Animales de Enfermedad , Transducción de Señal , Autofagia
15.
Biomed Pharmacother ; 164: 114948, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37257224

RESUMEN

Prostate cancer (PCa) is the most prevalent men's cancer in America and Western countries. No effective therapies are currently available for PCa aggressiveness, including castration-resistant progression (CRPC). This study aims at evaluation of the prospective efficacy and the molecular mechanism of scandenolone (SCA), a natural isoflavone, in PCa progression. SCA suppressed cell viability and progression and induced apoptosis in PCa cells. SCA inhibited the expression of lipogenesis and cholesterogenesis related key genes. Through inhibition of these metabolic genes, SCA decreased the levels of fatty acids, lipid droplets and cholesterols in PCa cells. Moreover, SCA enhanced the expression of antioxidant factors, including Nrf2, HO-1, catalase and SOD-1, and reduced the ROS levels in PCa cells. Substantially, SCA displayed the potential efficacy on CRPC tumors. This paper offers a new insight into the underlying molecular basis of SCA in PCa cells. By coordinated impairment of the metabolic and signaling vulnerabilities, including lipogenesis, cholesterogenesis, ROS and the AR/PSA axis, SCA could be applied as a novel and promising remedy to cure malignant PCa.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estudios Prospectivos , Apoptosis , Línea Celular Tumoral
16.
Heliyon ; 9(11): e20795, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37954385

RESUMEN

We explored the effects of different conditions on the artificial incubation of redclaw crayfish eggs in an effort to improve this process. Samples at the egg and juvenile stages were selected. The samples at different stages were separated from the pleopods, then they were placed in incubator boxes and sterilized with different disinfectant solutions. The density was 300,400 and 500 eggs/incubator box, the vibration frequency was 11,16 and 26 vibrations/min, and the water circulation cycle was 2.1, 4.8 and 7.1 cycles/h. The results showed the eggs disinfected with 3000 ppm formaldehyde for 15 min had stronger antioxidant capacity. The hatching and survival rates of five pairs of appendage stage group were significantly lower than those of other groups. In the egg stage, acid phosphatase (ACP) level of compound eye pigmentation stage group was significantly higher than those of other groups. In the juvenile stage, malondialdehyde (MDA) content of five pairs of appendage stage group was significantly higher than those of other groups. The survival rate of 500 eggs/box group was significantly higher than that of other groups. In the egg stage, alkaline phosphatase (AKP) level of 400 eggs/box group was significantly higher than that of other groups. The survival rate of 11 vibrations/min group was significantly higher than that of other groups. In the egg stage, ACP and AKP levels of 11 vibrations/min group were significantly higher than those of 26 vibrations/min group. In the juvenile stage, superoxide dismutase (SOD), ACP and AKP levels of 11 vibrations/min group was significantly higher than those of 26 vibrations/min group. In the juvenile stage, AKP level of 4.8 cycles/h group was significantly lower than that of other groups. In conclusion, egg development at the stage after seven pairs of appendages, with a density of 400 eggs/box, vibration frequencies set at 11 vibrations/min achieved high hatching rates (93.58 %) and survival rates (75.67 %). Moreover, bronopol or hydrogen peroxide might have a better choice to replace formaldehyde if further exploration was conducted to reduce stimulation of the in vitro-grown egg. These conditions could be used on a large scale to optimize the production of redclaw crayfish.

17.
Life (Basel) ; 12(11)2022 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-36362924

RESUMEN

Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies for the lethal PCa diseases is currently an urgent need. In this study, we endeavored to investigate the therapeutic efficacy of alpinumisoflavone (AIF), a natural product, in PCa. LNCaP (androgen- sensitive) and C4-2 (CRPC) PCa cells were used. An MTT-based method, soft agar colony forming assay, biological progression approaches were applied to determine cell viability, migration, and invasion. A fatty acid quantification kit, a cholesterol detection kit and oil red O staining were conducted to analyze the intracellular levels of lipids and cholesterols. Apoptosis assays were also performed. AIF reduced cell viability, migration, and invasion in PCa cells. The expression of androgen receptor (AR), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was substantially inhibited by AIF treatment in PCa cells. Furthermore, by inhibiting FASN and HMGCR expression, AIF decreased the amounts of intracellular fatty acids, cholesterols, and lipid droplets in PCa cells. Significantly, through coordinated targeting FASN- and HMGCR-regulated biosynthesis and the AR axis, AIF activated the caspase-associated apoptosis in PCa cells. These results collectively demonstrated for the first time the potential of AIF as a novel and attractive remedy and provided an alternative opportunity to cure PCa malignancy.

18.
Biomed Pharmacother ; 153: 113434, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36076488

RESUMEN

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has led to the most severe global pandemic, which began in Wuhan, China. Angiotensin-converting enzyme 2 (ACE2) combines with the spike protein of SARS-CoV-2, allowing the virus to cross the membrane and enter the cell. SARS-CoV-2 is modified by the transmembrane protease serine 2 (TMPRSS2) to facilitate access to cells. Accordingly, ACE2 and TMPRSS2 are targets of vital importance for the avoidance of SARS-CoV-2 infection. Sanghuangporus sanghuang (SS) is a traditional Chinese medicine that has been demonstrated to have antitumor, antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective and immunomodulatory properties. In this paper, we demonstrated that SS decreased ACE2 and TMPRSS2 expression in cell lines and a mouse model without cytotoxicity or organ damage. Liver and kidney sections were confirmed to have reduced expression of ACE2 and TMPRSS2 by immunohistochemistry (IHC) assessment. Then, hispidin, DBA, PAC, PAD and CA, phenolic compounds of SS, were also tested and verified to reduce the expression of ACE2 and TMPRSS2. In summary, the results indicate that SS and its phenolic compounds have latent capacity for preventing SARS-CoV-2 infection in the future.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Tratamiento Farmacológico de COVID-19 , Animales , Basidiomycota , Ratones , Ratones Endogámicos DBA , Peptidil-Dipeptidasa A/metabolismo , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/metabolismo
19.
Curr Med Chem ; 2022 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35702778

RESUMEN

BACKGROUND: Type-2 diabetes is a chronic progressive metabolic disease resulting in severe vascular complications and mortality risk. Recently, DPP-4 inhibitors are conceived as a favorable class of agents for the treatment of type 2 diabetes due to the minimal side effects. METHODS: Sitagliptin is the first medicine approved for DPP-4 inhibitor. Its structure involved three fragments: 2,4,5-triflorophenyl fragment pharmacophore, enantiomerically ß-amino carbonyl linker, and tetrahydrotriazolopyridine. Herein, we are drawn to the possibility of substituting tetrahydrotriazolopyridine motif present in Sitagliptin with a series of new fused pyrazolopyrimidine bicyclic fragment to investigate potency and safety. RESULTS: Two series of fused 6-(aminomethyl)pyrazolopyrimidine and 6-(hydroxymethyl)pyrazolopyrimidine derivatives containing ß-amino ester or amide as linkers were successfully designed for the new DPP-4 inhibitors. Most fused 6-methylpyrazolopyrimidines were evaluated against DPP-4 inhibition and selectivity capacity. Based on research study, ß-amino carbonyl fused 6-(hydroxymethyl)pyrazolopyrimidine possesses the significant DPP-4 inhibition (IC50 ≤ 59.8 nM) and presents similar with Sitagliptin (IC50 = 28 nM). Particularly, they had satisfactory selectivity over DPP-8 and DPP-9, except for QPP. CONCLUSION: ß-Amino esters and amides fused 6-(hydroxymethyl)pyrazolopyrimidine were developed as the new DPP-4 inhibitors. Those compounds with a methyl group or hydrogen in N-1 position and methyl substituted group in C-3 of pyrazolopyrimidine moiety showed better potent DPP-4 inhibition (IC50 = 21.4-59.8 nM). Furthermore, they had satisfactory selectivity over DPP-8 and DPP-9 Finally, the docking results revealed that compound 9n was stabilized at DPP-4 active site and would be a potential lead drug.

20.
Biomater Adv ; 133: 112597, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35525753

RESUMEN

Curcumin is proven to have potent anti-inflammatory activity, but its low water solubility and rapid degradation in physiological conditions limit its clinical use, particularly in intravenous drug delivery. In this study, we fabricated rod-shaped, acid-labile nanogels, using high biosafe and biocompatible polymers, for intravenous application in systemic inflammation treatment. The constituent polymers of the nanogels were prepared via the conjugation of vitamin B6 derivatives, including pyridoxal and pyridoxamine, onto poly(glutamate) with ester bonds. The aldehyde groups of the pyridoxal and amine groups of the pyridoxamine on the polymers enable crosslinking using a Schiff base during the solvent evaporation procedure for the preparation of the rod-shaped nanogels. Our study is the first to introduce this linkage, which is generated from two vitamin B6 derivatives into a nanogel system. It is also the first to fabricate a rod-shaped nanogel system via simple solvent evaporation. Under acidic conditions, such as those encountered in the endosomes and lysosomes within inflammatory macrophage cells spread in the whole body, imine bonds are cleaved and release payloads. The nanogel polymers were successfully synthesized and characterized, and the formation and disappearance of the Schiff base under neutral and acidic conditions were also confirmed using Fourier transform infrared spectroscopy. Following curcumin encapsulation, the long, rod-shaped nanogels were able to rapidly internalize into macrophage cells in static or adhere to cells under the flows, release their payloads in the acid milieus, and, thus, mitigate curcumin degradation. Consequently, curcumin-loaded, rod-shaped nanogels displayed exceptional anti-inflammatory activity both in vitro and in vivo, by efficiently inhibiting pro-inflammatory mediator secretion. These results demonstrate the feasibility of our acid-labile, rod-shaped nanogels for the treatment of systemic inflammation.


Asunto(s)
Curcumina , Curcumina/farmacología , Humanos , Inflamación/tratamiento farmacológico , Nanogeles , Polietilenglicoles , Polietileneimina , Polímeros/química , Piridoxal , Piridoxamina , Bases de Schiff , Solventes , Vitaminas
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