RESUMO
Garcinia kola is a medicinal food commonly consumed in Sub-Sahara Africa, for which Kolaviron (KV) is the active portion. As a follow-up to our earlier chemopreventive studies, we investigated the chemotherapeutic effects of KV on experimentally induced mammary carcinogenesis in female Wistar rats. Mammary carcinogenesis was induced using 80 mg/kg of 7,12-dimethylbenzanthracene (DMBA) administered by oral gavage. One hundred-fifty days post-DMBA induction, estrogen receptor-α (ER-α) levels were determined in the experimental rats before treatment with KV commenced. Treatment was done using 50, 100, and 200 mg/kg KV thrice a week for 4 weeks, after which the experiment was terminated. Significantly higher levels of estrogen receptor-α, CYP 1A1, malondialdehyde, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased cytokine (interleukin-6 and tumor necrosis factor-α) activity were observed in DMBA-induced rats, which were attenuated in KV-treated rats. Tyrosine metabolism was exclusively enriched in DMBA-induced rats in contrast to KV-treated rats. Collectively, the results point to the chemotherapeutic potential of KV.
RESUMO
A drug is any substance capable of altering the functioning of a person's body and mind. In this paper, a deterministic nonlinear model was adapted to investigate the behavior of drug abuse and addiction that incorporates intervention in the form of awareness and rehabilitation. In the mathematical analysis part, the positivity and boundedness of the solution and the existence of drug equilibria have been ascertained, which shows that the model consists of two equilibria: a drug-free equilibrium and a drug endemic equilibrium point. The drug-free equilibrium was found to be both globally and locally asymptotically stable if the effective reproduction number is less than or equal to one (Rc≤1). Furthermore, we were able to show the existence of a unique drug endemic equilibrium whenever Rc>1. Global asymptotic stability of a drug endemic equilibrium point has been ascertained using a nonlinear Lyapunov function of Go-Volterra type, which reveals that the drug endemic equilibrium point is globally asymptotically stable if an effective reproduction number is greater than unity and if there is an absence of a reversion rate of mended individuals (i.e., ω=0). In addition, an optimal control problem was formulated to investigate the optimal strategy for curtailing the spread of the behavior using control variables. The control variables are massive awareness and rehabilitation intervention of both public and secret addicted individuals. The optimal control simulation shows that massive awareness control is the best to control drug addiction in a society. In sensitivity analysis section, the proportion of those who are exposed publicly shows to be a must sensitive parameter that can reduce the reproduction number, and the effective contact rate shows to be a must sensitive parameter to increase the reproduction number. Numerical simulations reveal that the awareness rate of exposed publicly and the rehabilitation rate of addicted publicly are very important parameters to control drug addiction in a society.
Assuntos
Transtornos Relacionados ao Uso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Humanos , Conscientização , Dinâmica não Linear , Modelos Teóricos , Simulação por ComputadorRESUMO
Plant-derived phytochemicals from medicinal plants are becoming increasingly attractive natural sources of antimicrobial and antiviral agents due to their therapeutic value, mechanism of action, level of toxicity and bioavailability. The continued emergence of more immune-evasive strains and the rate of resistance to current antiviral drugs have created a need to identify new antiviral agents against SARS-CoV-2. This study investigated the antiviral potential of balsaminol, a bioactive compound from Momordica balsamina, and its inhibitory activities against SARS-CoV-2 receptor proteins. In this study, three Food and Drug Administration (FDA) COVID-19 approved drugs namely; nirmatrelvir, ritonavir and remdesivir were used as positive control. Molecular docking was performed to determine the predominant binding mode (most negative Gibbs free energy of binding/ΔG) and inhibitory activity of balsaminol against SARS-CoV-2 receptor proteins. The pharmacokinetics, toxicity, physicochemical and drug-like properties of balsaminol were evaluated to determine its potential as an active oral drug candidate as well as its non-toxicity in humans. The results show that balsaminol E has the highest binding affinity to the SARS CoV-2 papain-like protease (7CMD) with a free binding energy of - 8.7 kcal/mol, followed by balsaminol A interacting with the spike receptor binding domain (6VW1) with - 8.5 kcal/mol and balsaminol C had a binding energy of - 8.1 kcal/mol with the main protease (6LU7) comparable to the standard drugs namely ritonavir, nirmatrelvir and remdesivir. However, the ADMET and drug-like profile of balsaminol F favours it as a better potential drug candidate and inhibitor of the docked SARS-CoV-2 receptor proteins. Further preclinical studies are therefore recommended. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00241-0.
RESUMO
Background: Faidherbia albida, popularly known as gawo in Hausa, is traditionally used to treat jaundice in Zuru emirate of Kebbi State. Herein, the ameliorative effect of F. albida against 2.4-dinitrophenylhydrazine-induced hyperbilirubinemia in Wistar albino rats was investigated. Methods: Thirty healthy rats were administered 75 mg of 2.4-dinitrophenylhydrazine to induce hyperbilirubinemia. Thereafter, groups 1-3 received 500, 750, and 1000 mg/kg body weight of the methanol stem-bark extract, and 15 mg/kg of phenobarbitone (standard drug) was administered to group 4. Groups 5 and 6 served as the untreated and normal controls, respectively. The phytochemical composition was evaluated using standard methods, and acute oral toxicity was evaluated using standard OECD 2008 guidelines. Results: Phytochemical analysis revealed the presence of alkaloids, phenols, and a substantial amount of tannins. A significant (P<0.05) reduction of direct bilirubin, total bilirubin, and total protein levels for all the doses of the extract and standard drug compared to untreated groups was observed. Similarly, there were significant reductions in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels of the group treated with the standard drug and all extract-treated groups compared to elevated levels observed in untreated controls. However, a significant (P<0.05) increase in serum albumin (ALB) levels, red blood cells, hemoglobin, and pack cell volume was observed in all extract-treated compared to the untreated control in contrast to a significant decrease in MCH levels in treated groups compared to the untreated group. Conclusion: F. albida ameliorated the hyperbilirubinemia induced by 2.4-dinitrophenylhydrazine in Wistar albino rats, thus providing some support for its use in traditional medicine to treat jaundice.
RESUMO
Type 1 diabetes (T1D) affects gastrointestinal (GI) motility, favoring gastroparesis, constipation, and fecal incontinence, which are more prevalent in women. The mechanisms are unknown. Given the G-protein-coupled estrogen receptor's (GPER) role in GI motility, we investigated sex-related diabetes-induced epigenetic changes in GPER. We assessed GPER mRNA and protein expression levels using qPCR and Western blot analyses, and quantified the changes in nuclear DNA methyltransferases and histone modifications (H3K4me3, H3Ac, and H3K27Ac) by ELISA kits. Targeted bisulfite and chromatin immunoprecipitation assays were used to evaluate DNA methylation and histone modifications around the GPER promoter by chromatin immunoprecipitation assays in gastric and colonic smooth muscle tissues of male and female control (CTR) and non-obese diabetic (NOD) mice. GPER expression was downregulated in NOD, with sex-dependent variations. In the gastric smooth muscle, not in colonic smooth muscle, downregulation coincided with differences in methylation ratios between regions 1 and 2 of the GPER promoter of NOD. DNA methylation was higher in NOD male colonic smooth muscle than in NOD females. H3K4me3 and H3ac enrichment decreased in NOD gastric smooth muscle. H3K4me3 levels diminished in the colonic smooth muscle of NOD. H3K27ac levels were unaffected, but enrichment decreased in NOD male gastric smooth muscle; however, it increased in the NOD male colonic smooth muscle and decreased in the female NOD colonic smooth muscle. Male NOD colonic smooth muscle exhibited decreased H3K27ac levels, not female, whereas female NOD colonic smooth muscle demonstrated diminished enrichment of H3ac at the GPER promoter, contrary to male NOD. Sex-specific epigenetic mechanisms contribute to T1D-mediated suppression of GPER expression in the GI tract. These insights advance our understanding of T1D complications and suggest promising avenues for targeted therapeutic interventions.
Assuntos
Colo , Metilação de DNA , Epigênese Genética , Histonas , Músculo Liso , Regiões Promotoras Genéticas , Receptores Acoplados a Proteínas G , Animais , Feminino , Masculino , Camundongos , Colo/metabolismo , Colo/patologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/genética , Histonas/metabolismo , Camundongos Endogâmicos NOD , Músculo Liso/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Estômago/patologiaRESUMO
Type 2 diabetes mellitus (T2D) causes gastroparesis, delayed intestinal transit, and constipation, for unknown reasons. Complications are predominant in women than men (particularly pregnant and postmenopausal women), suggesting a female hormone-mediated mechanism. Low G-protein coupled estrogen receptor (GPER) expression from epigenetic modifications may explain it. We explored sexually differentiated GPER expression and gastrointestinal symptoms related to GPER alterations in wild-type (WT) and T2D mice (db/db). We also created smooth muscle-specific GPER knockout (GPER KO) mice to phenotypically explore the effect of GPER deficiency on gastrointestinal motility. GPER mRNA and protein expression, DNA methylation and histone modifications were measured from stomach and colon samples of db/db and WT mice. Changes in gut motility were also evaluated as daily fecal pellet production patterns. We found that WT female tissues have the highest GPER mRNA and protein expressions. The expression is lowest in all db/db. GPER downregulation is associated with promoter hypermethylation and reduced enrichment of H3K4me3 and H3K27ac marks around the GPER promoter. We also observed sex-specific disparities in fecal pellet production patterns of the GPER KO mice compared to WT. We thus, conclude that T2D impairs gut GPER expression, and epigenetic sex-specific mechanisms matter in the downregulation.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Masculino , Camundongos , Feminino , Humanos , Animais , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Experimental/genética , Estrogênios , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Músculo Liso/metabolismo , Epigênese Genética , RNA MensageiroRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is associated with a high mortality rate due to early recurrence and its metastasis features. To this day, effective treatment options for metastatic HCC remain a major challenge to patient treatment. Flavokawain B (FKB) is a naturally occurring chalcone molecule capable of providing effective therapy against this life-threatening disease. OBJECTIVE: This study investigated the anti-metastatic effects of FKB on the growth and development of metastatic HCC. METHODS: HepG2 cells were used in this study and a neutral red assay was performed to determine the IC50 value of FKB. Cell scratch and exclusion zone assays were performed to assess the rate of cell migration and invasion. Relative mRNA levels of UCK2, STAT3, VEGF and HIF-1α genes were quantified using RT-qPCR. RESULTS: FKB inhibited the proliferation of HepG2 cells at an IC50 value of 28 µM after 72 h of incubation. Its cytotoxic effect was confirmed to induce apoptosis through the phase-contrast inverted microscope. Cell migration and invasion were significantly inhibited at 7, 14, and 28 µM of FKB as compared to untreated cells. The inhibition in the cell migration significantly increased with the increasing concentrations of the bioactive compound. The relative expression levels of the UCK2 gene and its downstream genes, STAT3, VEGF and HIF-1α, were significantly downregulated after 72 h exposure to FKB treatment. CONCLUSION: Our data suggest that FKB inhibited HepG2 proliferation and further suppressed its metastasis partly by regulating the STAT3/Hif-1α/VEGF signalling pathway. FKB could be a potential alternative and viable strategy against HCC.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Linhagem Celular Tumoral , Uridina Quinase , Fator de Transcrição STAT3/farmacologiaRESUMO
Bacterial spores are metabolically inactive and highly resistant to harsh environmental conditions in nature and during decontamination processes in food and related industries. However, inducing germination using specific germinants in dormant spores can convert them into vegetative cells which are metabolically active and fragile. The potential utility of a "germinate to eradicate" strategy, also known as germination-inactivation, has been validated in foods. Meanwhile, the strategy has sparked much interest in triggering and maximizing spore germination. Although many details of the spore germination process have been identified over the past decades, there remain many uncertainties, including some signal transduction mechanisms involved in germination. In addition, the successful implementation of the germination-inactivation strategy relies on the sensitive detection of germinative biomarkers within minutes of germination initiation and the optimal timing for the subsequent inactivation step. Meanwhile, the emergence of biomarkers has renewed attention to the practical application of the spore germination process. Here, this review presents the current knowledge of the germination mechanisms of Bacillus spore, influencing factors, and germination biomarkers. It also covers a detailed discussion on the development of germination-inactivation as a spore eradication strategy.
RESUMO
Prostate cancer is a leading cause of morbidity and mortality among men globally. In this study, we employed an in silico approach to predict the possible mechanisms of action of selected novel compounds reported against prostate cancer epigenetic targets and their derivatives, exhausting through ADMET profiling, drug-likeness, and molecular docking analyses. The selected compounds: sulforaphane, silibinin, 3, 3'-diindolylmethane (DIM), and genistein largely conformed to ADMET and drug-likeness rules including Lipinski's. Docking studies revealed strong binding energy of sulforaphane with HDAC6 (- 4.2 kcal/ mol), DIM versus HDAC2 (- 5.2 kcal/mol), genistein versus HDAC6 (- 4.1 kcal/mol), and silibinin against HDAC1 (- 7.0 kcal/mol) coupled with improved binding affinities and biochemical stabilities after derivatization. Findings from this study may provide insight into the potential epigenetic reprogramming mechanisms of these compounds against prostate cancer and could pave the way toward more success in prostate cancer phytotherapy.
RESUMO
Onchocerciasis is a vector-borne disease caused by the filarial nematode Onchocerca volvulus, which is responsible for most of the visual impairments recorded in Africa, Asia and the Americas. It is known that O. volvulus has similar molecular and biological characteristics as Onchocerca ochengi in cattle. This study was designed to screen for immunogenic epitopes and binding pockets of O. ochengi IMPDH and GMPR ligands using immunoinformatic approaches. In this study, a total of 23 B cell epitopes for IMPDH and 7 B cell epitopes for GMPR were predicted using ABCpred tool, Bepipred 2.0 and Kolaskar and Tongaonkar methods. The CD4+ Th computational results showed 16 antigenic epitopes from IMPDH with strong binding affinity for DRB1_0301, DRB3_0101, DRB1_0103 and DRB1_1501 MHC II alleles while 8 antigenic epitopes from GMPR were predicted to bind DRB1_0101 and DRB1_0401 MHC II alleles, respectively. For the CD8+ CTLs analysis, 8 antigenic epitopes from IMPDH showed strong binding affinity to human leukocyte antigen HLA-A*26:01, HLA-A*03:01, HLA-A*24:02 and HLA-A*01:01 MHC I alleles while 2 antigenic epitopes from GMPR showed strong binding affinity to HLA-A*01:01 allele, respectively. The immunogenic B cell and T cell epitopes were further evaluated for antigenicity, non-alllergernicity, toxicity, IFN-gamma, IL4 and IL10. The docking score revealed favorable binding free energy with IMP and MYD scoring the highest binding affinity at -6.6 kcal/mol with IMPDH and -8.3 kcal/mol with GMPR. This study provides valuable insight on IMPDH and GMPR as potential drug targets and for the development of multiple epitope vaccine candidates.Communicated by Ramaswamy H. Sarma.
Assuntos
Onchocerca , Vacinas , Humanos , Animais , Bovinos , Onchocerca/metabolismo , Imunoinformática , GMP Redutase/química , GMP Redutase/metabolismo , IMP Desidrogenase/química , IMP Desidrogenase/metabolismo , Epitopos de Linfócito B , Epitopos de Linfócito T , Guanosina , Inosina , Antígenos HLA-ARESUMO
As trypanocide, several side effects have been reported in the use of Isometamidium chloride. This study was therefore, designed to evaluate its ability to induce oxidative stress and DNA damage using D. melanogaster as a model organism. The LC50 of the drug was determined by exposing the flies (1-3 days old of both genders) to six different concentrations (1 mg, 10 mg, 20 mg, 40 mg, 50 mg and 100 mg per 10 g of diet) of the drug for a period of seven days. The effect of the drug on survival (28 days), climbing behavior, redox status, oxidative DNA lesion, expression of p53 and PARP1 (Poly-ADP-Ribose Polymerase-1) genes after five days exposure of flies to 4.49 mg, 8.97 mg, 17.94 mg and 35.88 mg per 10 g diet was evaluated. The interaction of the drug in silico with p53 and PARP1 proteins was also evaluated. The result showed the LC50 of isometamidium chloride to be 35.88 mg per 10 g diet for seven days. Twenty-eight (28) days of exposure to isometamidium chloride showed a decreased percentage survival in a time and concentration-dependent manner. Isometamidium chloride significantly (p < 0.05) reduced climbing ability, total thiol level, Glutathione-S-transferase, and Catalase activity. The level of H2O2 was significantly (p < 0.05) increased. The result also showed significant (p < 0.05) reduction in the relative mRNA levels of p53 and PARP1 genes. The in silico molecular docking of isometamidium with p53 and PARP1 proteins showed high binding energy of -9.4 Kcal/mol and -9.2 Kcal/mol respectively. The results suggest that isometamidium chloride could be cytotoxic and a potential inhibitor of p53 and PARP1 proteins.
RESUMO
Introduction: For decades, viral diseases have been treated using medicinal plants and herbal practices in the northern part of Nigeria. Though scarcely investigated, these medicinal plants could serve as potential sources for novel antiviral drugs against emerging and remerging viral diseases. Therefore, this study is aimed at investigating the medicinal practices and plants used to treat emerging and re-emerging viral diseases including hepatitis, poliomyelitis, monkeypox, smallpox, yellow fever, Lassa fever, meningitis, and COVID-19 in some northern states; Katsina, Kebbi, Kwara and Sokoto states. Method: Administered questionnaires and oral interviews were used to collect information on medicinal plants, method of preparation of herbal formulations, diagnosis, and treatment of viral diseases. Medicinal plants were collected, botanically identified, and assigned voucher numbers. The plant names were verified using www.theplantlist.org, www.worldfloraonline.org and the international plant names index. Result: A total of 280 participating herbal medicine practitioners (HMPs) mentioned 131 plants belonging to 65 families. Plant parts such as roots, bark, leaf, seed, and fruit were prepared as a decoction, concoction, infusion, or ointment for oral and topical treatment of viral diseases. Moringa oleifera (75.3%), Elaeis guineensis Jacq. (80%), and Acacia nilotica (70%) were the most frequently mentioned plants in Kebbi, Kwara and Sokoto states, respectively. Conclusion: The study revealed scarcely investigated and uninvestigated medicinal plants used to treat hepatitis, poliomyelitis, monkeypox, smallpox, yellow fever, Lassa fever, meningitis, and COVID-19. Future studies should be conducted to determine the antiviral potency and isolate novel bioactive agents from these plants against viral diseases.
RESUMO
For many patients, diabetes Mellitus and Malignancy are frequently encountered comorbidities. Diabetes affects approximately 10.5% of the global population, while malignancy accounts for 29.4 million cases each year. These troubling statistics indicate that current treatment approaches for these diseases are insufficient. Alternative therapeutic strategies that consider unique signaling pathways in diabetic and malignancy patients could provide improved therapeutic outcomes. The G-protein-coupled estrogen receptor (GPER) is receiving attention for its role in disease pathogenesis and treatment outcomes. This review aims to critically examine GPER' s comparative role in diabetes mellitus and malignancy, identify research gaps that need to be filled, and highlight GPER's potential as a therapeutic target for diabetes and malignancy management. There is a scarcity of data on GPER expression patterns in diabetic models; however, for diabetes mellitus, altered expression of transport and signaling proteins has been linked to GPER signaling. In contrast, GPER expression in various malignancy types appears to be complex and debatable at the moment. Current data show inconclusive patterns of GPER expression in various malignancies, with some indicating upregulation and others demonstrating downregulation. Further research should be conducted to investigate GPER expression patterns and their relationship with signaling pathways in diabetes mellitus and various malignancies. We conclude that GPER has therapeutic potential for chronic diseases such as diabetes mellitus and malignancy.
Assuntos
Diabetes Mellitus , Neoplasias , Humanos , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Estrogênios , Diabetes Mellitus/metabolismo , Proteínas de Ligação ao GTP/metabolismoRESUMO
We previously found that QNBC tumors are more frequent in African Americans compared to TNBC tumors. To characterize this subtype further, we sought to determine the miRNA-mRNA profile in QNBC patients based on race. Both miRNA and mRNA expression data were analyzed from TCGA and validated using datasets from the METABRIC, TCGA proteomic, and survival analysis by KMPLOT. miRNA-mRNAs which include FOXA1 and MYC (mir-17/20a targets); GATA3 and CCNG2 (mir-135b targets); CDKN2A, CDK6, and B7-H3 (mir-29c targets); and RUNX3, KLF5, IL1-ß, and CTNNB1 (mir-375 targets) were correlated with basal-like and immune subtypes in QNBC patients and associated with a worse survival. Thus, QNBC tumors have an altered gene signature implicated in racial disparity and poor survival.
Assuntos
Neoplasias da Mama , MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Mama/genética , Neoplasias de Mama Triplo Negativas/patologia , Negro ou Afro-Americano/genética , Proteômica , RNA Mensageiro , Regulação Neoplásica da Expressão GênicaRESUMO
Arylsulfone groups play an important role in the synthesis of functionalized molecules. The acetonitrile-mediated three-component reactions for arylsulfone synthesis were developed in the presence of a 0.00025 mol % palladium catalyst. Arylboronic acids reacted with potassium metabisulfite (K2S2O5) and benzyl bromide in the presence of LiF and a very low concentration of PdCl2 in acetonitrile solvents to produce the corresponding benzyl arylsulfones in moderate to good yields. Various arylboronic acids reacted with K2S2O5 and carbon electrophiles to produce the desired arylsulfones under the optimized conditions. It was proposed that acetonitrile accelerated the generation of aryl anion species from the reaction of arylboronic acids and LiF.
RESUMO
Purpose: The purpose of the study was to determine how camel milk affects hyperglycemia, beta-cell function, oxidative stress, and inflammatory markers in type 2 diabetic pigs. Methods: Twenty-five (25) pigs were separated into five (5) groups of five pigs each, with five (5) non-diabetic and twenty (20) diabetic pigs in each group. Groups 1 and 2 received distilled water as the standard control and diabetic control groups, respectively, while Groups 3 and 4 received camel milk at 250 mL/day and 500 mL/day, respectively, and Group 5 received metformin at 500 mg/day. The experiment lasted ten weeks. At the end of the ten weeks, all the pigs were euthanized. Results: Treatments with camel milk substantially enhance glucose fasting levels by reducing hyperglycemia in diabetic pigs, significant level at (p < 0.05). When pigs given camel milk were compared with untreated diabetic pigs, there was a substantial rise (p < 0.05) in superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels. Also, camel milk substantially lowered the levels of interleukin (IL-1ß) and tumour necrosis factor-alpha (TNF-α) in diabetic pig serum. Similarly, immunohistochemical analysis of islet cells revealed an increase in insulin production, implying improved glycemic control and the eventual commitment of glucose to glycolysis. Conclusion: The bioactive-mediated anti-hyperglycemic and insulin release potential of camel milk treatments contributed to improving type 2 diabetes mellitus. Camel milk improved beta-cell function while reducing oxidative stress and inflammation in type 2 diabetic pigs.
RESUMO
Background: The presence of diabetes mellitus (DM) among COVID-19 patients is associated with increased hospitalization, morbidity, and mortality. Evidence has shown that hyperglycemia potentiates SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and plays a central role in severe COVID-19 and diabetes comorbidity. In this review, we explore the therapeutic potentials of herbal medications and natural products in the management of COVID-19 and DM comorbidity and the challenges associated with the preexisting or concurrent use of these substances. Methods: Research papers that were published from January 2016 to December 2021 were retrieved from PubMed, ScienceDirect, and Google Scholar databases. Papers reporting clinical evidence of antidiabetic activities and any available evidence of the anti-COVID-19 potential of ten selected natural products were retrieved and analyzed for discussion in this review. Results: A total of 548 papers (73 clinical trials on the antidiabetic activities of the selected natural products and 475 research and review articles on their anti-COVID-19 potential) were retrieved from the literature search for further analysis. A total of 517 articles (reviews and less relevant research papers) were excluded. A cumulative sum of thirty-one (31) research papers (20 clinical trials and 10 others) met the criteria and have been discussed in this review. Conclusion: The findings of this review suggest that phenolic compounds are the most promising phytochemicals in the management of COVID-19 and DM comorbidity. Curcumin and propolis have shown substantial evidence against COVID-19 and DM in humans and are thus, considered the best potential therapeutic options.
RESUMO
Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.
When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.
Assuntos
Neoplasias de Mama Triplo Negativas , Metilação de DNA , Epigênese Genética , Epigenômica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Cytokine storm is a phrase used to refer to an abrupt upsurge in the circulating levels of various pro-inflammatory cytokines, causing increased stimulation and activity of immune cells during disease conditions. The binding of pattern recognition receptors to pathogen-associated molecular patterns during COVID-19 infection recruits response machinery involving the activation of transcription factors and proteins required for a robust immune response by host cells. These immune responses could be influenced by epigenetic modifications as evidenced by significant variations in COVID-19 pathophysiology and response to therapy observed among patients across the globe. Considering that circulating levels of interleukin 1, tumor necrosis factor-α, and interleukin 6 are significantly elevated during cytokine storm in COVID-19 patients, genetic and epigenetic variations in the expression and function of these proteins could enhance our understanding of the disease pathogenesis. Treatment options that repress the transcription of specific cytokine genes during COVID-19 infection could serve as possible targets to counteract cytokine storm in COVID-19. Therefore, the present article reviews the roles of cytokines and associated genes in the COVID-19 cytokine storm, identifies epigenetic modifications associated with the disease progression, and possible ameliorative effects of some vitamins and minerals obtained as epigenetic modifiers for the control of cytokine storm and disease severity in COVID-19 patients. PRACTICAL APPLICATIONS: COVID-19 causes mortality and morbidity that adversely affect global economies. Despite a global vaccination campaign, side effects associated with vaccination, misconceptions, and a number of other factors have affected the expected successes. Cytokine storm in COVID-19 patients contributes to the disease pathogenesis and response to therapy. Epigenetic variations in the expression of various cytokines could be implicated in the different outcomes observed in COVID-19 patients. Certain vitamins and minerals have been shown to interfere with the expression and activity of cytokines implicated in cytokine storm, thereby counteracting observed pathologies. This review examines cytokines implicated in cytokine storm in COVID-19, epigenetic modifications that contribute to increased expression of identified cytokines, specific foods rich in the identified vitamins and minerals, and suggests their possible ameliorative benefits. The article will be beneficial to both scientists and the general public who are interested in the role of vitamins and minerals in ameliorating COVID-19.