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1.
Nutrients ; 16(14)2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39064796

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn's disease (CD) or ulcerative colitis (UC). Despite substantial advances in understanding the underlying causes of IBD, the available treatments remain restricted and are sometimes accompanied by severe consequences. Consequently, there is an urgent need to study alternate therapeutic options. This review assesses the present drugs, identifies their limitations, and proposes the use of saffron, a natural plant with great therapeutic potential based on preclinical and clinical investigations. Saffron has gained attention for its potential therapeutic benefits in treating various ailments due to its established bioactive compounds possessing antioxidant and anti-inflammatory properties. This review covers how saffron impacts the levels of calprotectin, an inflammatory marker, for various inflammatory responses in multiple diseases including IBD. Data from clinical trials were assessed to determine the efficacy and safety of using saffron to counter inflammation in multiple diseases. Studies have shown that saffron may protect against inflammatory bowel disease (IBD) through several mechanisms by inhibiting pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), reducing oxidative stress through antioxidant effects, enhancing mucosal barrier function by upregulating tight junction proteins, and modulating the gut microbiota composition to promote beneficial bacteria while suppressing pathogenic ones; these combined actions contribute to its therapeutic potential in managing and alleviating the symptoms of IBD. This will enable future research endeavors and expedite the translation of saffron-based interventions into clinical practice as a valuable adjunctive therapy or a potential alternative to conventional treatments, thereby enhancing the quality of life for individuals suffering from inflammatory diseases including IBD.


Assuntos
Anti-Inflamatórios , Crocus , Doenças Inflamatórias Intestinais , Crocus/química , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Animais , Estresse Oxidativo/efeitos dos fármacos , Doença de Crohn/tratamento farmacológico , Citocinas/metabolismo , Fitoterapia
2.
Gene ; 927: 148695, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38945313

RESUMO

Breast cancer (BCa) is a prevalent form of cancer in women, exhibiting varying rates and distribution across different ethnic groups. Among these groups, African American (AA) women have the highest incidence of BCa and the lowest levels of Vitamin D (VD). Numerous studies have explored the connection between variations in the VDR gene and BCa risk, particularly in different populations, but research on the AA population remains limited. Epigenetic modifications, including specific microRNAs (miRNAs), can influence gene expression without altering the genetic code and have been implicated in cancer initiation and progression. Our hypothesis suggests that VDR gene variations may increase BCa risk in AA women and that changes in miRNA expression profiles could contribute to BCa development. Using data from the 1000 Genome Project, we identified five VDR gene variants with significant frequency differences between AA and European-American (EA) populations. We genotyped 404 African American BCa cases and controls for five variants using TaqMan® assays. SNPstats assessed their association with BCa risk. The rs1544410 variant's recessive model (A/A) showed a decreased BCa risk in AA (odds ratio 0.33, 95% CI: 0.15-0.73, p-value 0.0041). Conversely, the rs2853563 variant's recessive model (A/A) was linked to an increased BCa risk (odds ratio 4.04, 95% CI: 1.49-10.95, p-value 0.0022). We investigated miRNA expression influenced by VD in HCC1806 Triple-Negative Breast Cancer (TNBC) cell lines with the A/A allele for rs2853563. nCounter® Nanostring technology assessed miRNA profiles after calcitriol treatment. Our results indicated that calcitriol treatment led to reduced expression of six miRNAs, four of which are associated with tumor suppression in the presence of the AA genotype in TNBC cell lines. These findings suggest that specific VDR genotypes could have a potential effect on the miRNAs expression which could potentially serve as markers for cell proliferation in TNBC.


Assuntos
Negro ou Afro-Americano , Neoplasias da Mama , Predisposição Genética para Doença , MicroRNAs , Receptores de Calcitriol , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Negro ou Afro-Americano/genética , Neoplasias da Mama/genética , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Genótipo , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética
3.
Cureus ; 16(4): e58484, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38765419

RESUMO

BACKGROUND: The relationship between diet and the management of chronic illnesses is well established. However, it is unknown the extent to which people with chronic illnesses pay attention to nutritional information and act upon the information obtained. We evaluated the menu ordering practices of adults with chronic illnesses. METHODS: We analyzed the 2018 Health Information National Trends Survey (HINTS 5 Cycle 2). Our analytic cohort included 3,154 respondents (weighted population size=228,464,822) who answered questions regarding a personal history of diabetes, hypertension, heart disease, and obesity. They also answered questions about their nutritional habits regarding whether they noticed caloric information at fast-food or sit-down restaurants and how that information influenced their dietary choices. RESULTS: Among respondents with these chronic illnesses, only obese patients were significantly more likely to pay attention to caloric information (OR=1.56; 95%CI: 1.06-2.31). However, noticing the calorie information was not associated with ordering less calories among all categories of respondents with chronic illnesses. CONCLUSION: US adults with chronic illnesses do not pay sufficient attention to the calorie information of their diet. Furthermore, awareness of the calorie information did not influence their dietary choices. Healthcare professionals should incorporate dietary counseling into the management of chronic illnesses of their patients.

4.
Arch Intern Med Res ; 7(1): 27-41, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694760

RESUMO

Background and aim: Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities. Design Setting and participants: We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients. Results: Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=<0.001, OR=2.18), bilirubin (n=577, 12.9%, p=0.01) and low albumin levels (n=361, 19.1%, p=0.03) were associated with mortality. Multivariate analysis (adjusted for age, sex, race, geographic location) indicates that patients with asthma, COPD, cardiac disease, hypertension, diabetes mellitus, immunocompromised status, shortness of breath and cough possess higher odds of in-hospital mortality. Among laboratory parameters, patients with lymphocytopenia (OR2=2.50), lymphocytosis (OR2=1.41), and elevations of serum CRP (OR2=4.19), CPK (OR2=1.43), LDH (OR2=2.10), troponin (OR2=2.91), ferritin (OR2=1.88), AST (OR2=2.18), D-dimer (OR2=2.75) are more prone to death. Patients on glucocorticoids (OR2=1.49) and mechanical ventilation (OR2=9.78) have higher in-hospital mortality. Conclusion: These findings suggest that older age, male sex, AA race, and hospitalization in New York were associated with higher in-hospital mortality rates from COVID-19 in early pandemic stages. Other predictors of mortality included the presence of comorbidities, shortness of breath, cough elevated serum inflammatory markers, altered lymphocyte count, elevated AST, and low serum albumin. AA patients comprised a disproportionate share of COVID-19 death in the US during 2020 relative to other races/ethnicities.

5.
Transl Cancer Res ; 13(3): 1314-1322, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38617523

RESUMO

Background: Coronavirus disease 2019 (COVID-19) manifest differently depending on patients' background and pre-existing conditions. It remains unclear how African Americans with cancer have been affected in comparison to those without. In this study, we aim to identify demographic, clinical, and laboratory markers associated with mortality in COVID-19 patients with cancer. Methods: We reviewed all COVID-19 hospitalized patients' records from Dec. 2019 to Oct. 2021 at Howard University Hospital. Patients having a history of, or active, cancer were reviewed. Clinical, treatment, lab test values, and pathological data were extracted. Univariable and multivariable analyses were conducted on the entire cohort as well as on cases and controls separately, using SPSS software. Results: Out of 512 COVID-19 infected patients, 49 had cancer, either active or history of cancer (cases) and 463 COVID-19 were cancer-free (controls), allowing for comparison. African American race was predominant in both cases and controls, 83.7% and 66.7% respectively. Cancer patients were older than non-cancer patients (mean age: 70.6 vs. 56.3 years) and had an increased length of hospital stay (mean 13.9 vs. 9.4 days). Mortality is significantly higher among cancer patients (n=10, 20.4%, P=0.03) compared to non-cancer COVID-19 patients (n=41, 8.9%). Among cancer patients, breast cancer was more prevalent in females and prostate cancer in males (54% and 52%, respectively). A comparison of patients with active vs. previous cancer showed no significant difference in the clinical outcome, death vs. discharge (P=0.34). A higher reduction in albumin level in cancer cases, from the time of admission to day 5, was significantly associated with death during the hospital stay compared to those discharged (n=24, 49.0%, P<0.001). In controls, lymphopenia (n=436, 94.2%, P=0.05), aspartate aminotransferase (AST) (n=59, 12.7%, P=0.008) and albumin (n=40, 8.6%, P=0.02) have shown an association with increased mortality. Conclusions: Albumin level has an inverse relationship with clinical outcomes among all COVID-19 infected cancer patients. Reduction in albumin level during the hospital stay, particularly in COVID-19 cancer patients should be considered as a predictor of mortality. Further research with a large cohort size is needed to verify and identify other predictors of outcomes in COVID-19 patients with cancer.

6.
Neoplasia ; 49: 100970, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38281411

RESUMO

The maintenance of DNA sequence integrity is critical to avoid accumulation of cancer-causing mutations. Inactivation of DNA Mismatch Repair (MMR) genes (e.g., MLH1 and MSH2) is common among many cancers, including colorectal cancer (CRC) and is the driver of classic microsatellite instability (MSI) in tumors. Somatic MSH3 alterations have been linked to a specific form of MSI called elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) that is associated with patient poor prognosis and elevated among African American (AA) rectal cancer patients. Genetic variants of MSH3 and their pathogenicity vary among different populations, such as among AA, which are not well-represented in publicly available databases. Targeted exome sequencing of MSH3 among AA CRC samples followed by computational bioinformatic pipeline and molecular dynamic simulation analysis approach confirmed six identified MSH3 variants (c.G1237A, c.C2759T, c.G1397A, c.G2926A, c.C3028T, c.G3241A) that corresponded to MSH3 amino-acid changes (p.E413K; p.S466N; p.S920F; p.E976K; p.H1010Y; p.E1081K). All identified MSH3 variants were non-synonymous, novel, pathogenic, and show loss or gain of hydrogen bonding, ionic bonding, hydrophobic bonding, and disulfide bonding and have a deleterious effect on the structure of MSH3 protein. Some variants were located within the ATPase site of MSH3, affecting ATP hydrolysis that is critical for MSH3's function. Other variants were in the MSH3-MSH2 interacting domain, important for MSH3's binding to MSH2. Overall, our data suggest that these variants among AA CRC patients affect the function of MSH3 making them pathogenic and likely contributing to the development or advancement of CRC among AA. Further clarifying functional studies will be necessary to fully understand the impact of these variants on MSH3 function and CRC development in AA patients.


Assuntos
Negro ou Afro-Americano , Neoplasias Colorretais , Humanos , Negro ou Afro-Americano/genética , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Instabilidade de Microssatélites , Repetições de Microssatélites , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Proteína 3 Homóloga a MutS/genética , Proteína 3 Homóloga a MutS/metabolismo , Virulência
7.
Artigo em Inglês | MEDLINE | ID: mdl-38044960

RESUMO

Background: The prevalence of Barrett's esophagus (BE) in African Americans (AA) is uncertain. However, several potential risk factors, includes family history, male sex, ethnicity, chronic heartburn and acid reflux, age over 60, current or past smoking, and obesity are associated with BE. The aim of this study is to determine the incidence of BE in AA patients who underwent Esophageal Gastro Endoscopy (EGD). Methods: Medical and demographic data of 1,253 AA patients with various symptoms, including BE, Esophageal adenocarcinoma (EAC), esophageal squamous adenocarcinoma (SCC), hiatal hernia, H. pylori infection, Gastro-Esophageal Reflux Disease (GERD), Gastritis, and esophagitis, were collected from January 2004 to December 2014 at Howard University Hospital. Results: Among the 1,253 patients, the median age was 61 and 49% were male out of the total. The frequencies of EAC (p= 0.05), and SCC (p= 0.002) were significantly high in males, along with SCC frequency significantly increased with older age (p<0.001). Furthermore, esophageal polyps with hiatal hernia (p=0.008) and H. pylori (p=<0.001) were found to be associated with esophagitis, and its presence may contribute to the development of BE. Conclusion: The findings highlighted the high prevalence of GERD symptoms and pathologic gastritis along with EAC was less common than SCC and both types of esophageal cancer were associated with male gender and older age whereas, H. pylori infection was identified as a risk factor for pathologic gastritis in AA. Overall data emphasize the need for extensive research, increased awareness, diagnosis, and management of GERD, gastritis, and related conditions to uncover the underlying mechanisms and factors contributing to these conditions in the AA population.

8.
World J Methodol ; 13(4): 323-336, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37771866

RESUMO

BACKGROUND: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID). AIM: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations. METHODS: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae. RESULTS: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans. CONCLUSION: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

10.
Curr Issues Mol Biol ; 45(7): 5558-5574, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37504267

RESUMO

Despite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD and how the microbiome and metabolome play a role has not been explored extensively. We aimed to establish whether saffron treatment modulates the host microbiome and metabolic profile in experimental colitis. Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron in a dose of 20 mg/kg body weight or vehicle through daily gavage. On day 10, stool pellets from mice were collected and analyzed to assess saffron's effect on fecal microbiota and metabolites through 16S rRNA sequencing and untargeted primary metabolite analysis. Saffron treatment maintained gut microbiota homeostasis by counter-selecting pro-inflammatory bacteria and maintained Firmicutes/Bacteroides ratio, which was otherwise disturbed by DSS treatment. Several metabolites (uric acid, cholesterol, 2 hydroxyglutaric acid, allantoic acid, 2 hydroxyhexanoic acid) were altered significantly with saffron treatment in DSS-treated mice, and this might play a role in mediating saffron's colitis-mitigating effects. These data demonstrate saffron's therapeutic potential, and its protective role is modulated by gut microbiota, potentially acting through changes in metabolites.

11.
Nutrients ; 15(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37447291

RESUMO

Environmental exposures, particularly diet, play an important role in the prevention or exacerbation of illnesses, including gastrointestinal (GI) diseases [...].


Assuntos
Suplementos Nutricionais , Nutrigenômica , Dieta
12.
Artigo em Inglês | MEDLINE | ID: mdl-37500830

RESUMO

BACKGROUND AND AIM: Type 2 diabetes mellitus (DM) is a common comorbidity in the minority population and is associated with poor outcomes in COVID-19 patients. We hypothesized that COVID-19 patients with pre-existing diabetes mellitus are prone to fatal outcomes compared to non-diabetic patients. We aimed to illustrate the characteristics and outcomes and identify the risk factors for in-hospital mortality of COVID-19 patients with DM. METHODS: In this single-center retrospective study, electronic medical records of hospitalized patients with confirmed COVID-19 diagnosis at Howard University Hospital (HUH) from March 2020 to Dec 2021 were analyzed. Clinical, demographic, and serological information, as well as outcomes, were recorded and analyzed. RESULTS: Among 463 COVID-19 patients, 66.3% (n = 307) were African Americans (AA) and 35.9% (n = 166) had diabetes, with a mean age of 64 years. The majority of the diabetic patients were AA (n = 123, 74.1%) and had a higher mortality rate (n = 26, 74.3%) compared to others. Length of stay in the hospital is significantly more for the diabetic than for the non-diabetic patients (11.3 vs. 8.3 days, p = 0.03). A higher proportion of ICU admission (32.3% vs. 17.9%, p = < 0.001), intubation (17% vs. 11.7%, p = 0.04), and increased mortality (21.1% vs. 12.2%, p = 0.01) were identified in COVID-19 patients with DM than in those with no DM. Among DM patients, non-survivors were older (69.9 vs. 62.9 years). DM patients were more likely to have underlying hypertension (72.3% vs. 43.3%, p = < 0.001), obesity (44.8% vs. 32.1%, p = 0.007), chronic kidney disease (23.6 vs. 11.8%, p = 0.001), and cardiovascular disease (29.5% vs. 14.3%, p = 0.001) than the non-DM patients. HbA1C above 9%, indicating poorly controlled hyperglycemia, was associated with poor outcome among the DM subjects. AST (23.5% vs. 31.3%) and creatinine (61.4% vs. 37.9%) were significantly more elevated in DM COVID-19 patients (all p-values < 0.05). The levels of serum troponin (42.5% vs. 30.9%, p = 0.03), interleukin-6 (67.2 vs. 50%, p = 0.04), ferritin (65.6% vs. 44.6%, p = 0.03), procalcitonin (58.1% vs. 46.1, p = 0.03), and D-dimers (92.8% vs. 86.5%, p = 0.04) were significantly higher in DM patients as compared to those in non-DM COVID-19 patients, indicating more susceptibility of diabetic COVID-19 patients to coagulation dysfunction and inflammatory storm. CONCLUSION: The prevalence of DM is high among hospitalized COVID-19 patients in our cohort. While DM patients have a higher mortality rate and ICU admission than non-DM patients, other factors such as underlying comorbidities, old age, elevated creatinine, AST, serum inflammatory markers, and D-dimer are more significant predictors of fatal outcomes. DM patients had higher metabolic derangements, hypercoagulability, and severe inflammatory response. No significant difference of outcome was noted between DM patients of different races in our cohort. In the diabetic group, it appears that race may not significantly contribute to the observed mortality disparity. This could be attributed to the significant influence of diabetes, which acts as a major effector, potentially overshadowing the significance of race in this context.

13.
PLoS One ; 18(6): e0286297, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37352211

RESUMO

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Estudos Observacionais como Assunto , Síndrome de COVID-19 Pós-Aguda , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Adolescente , Adulto , Estudos Multicêntricos como Assunto
14.
Nutrients ; 16(1)2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38201944

RESUMO

Prostate cancer is the most common cancer and the second leading cause of cancer deaths among men in the USA. Several studies have demonstrated the antitumor properties of saffron in different types of cancers, including prostate cancer. The oral administration of saffron extract has been reported to have antitumor effects on aggressive prostate-cancer-cell-line-derived xenografts in nude male mice. The objective of this study was to carry out in vitro studies of saffron-treated prostate cancer cells to ascertain the effects of saffron on key intermediates in prostate carcinogenesis. Our studies demonstrated the significant inhibition of cell proliferation for androgen-sensitive prostate cancer cell lines via apoptotic pathways. We also demonstrate the statistically significant down-regulation of DNA methyltransferases (COMT, MGMT, EHMT2, and SIRT1 deacetylase) in saffron-treated prostate cancer cells. In addition, saffron-treated prostate cancer cells displayed a statistically significant dysregulation of DNA repair intermediates (WRN, p53, RECQ5, MST1R, and WDR70) in a time-dependent manner. Furthermore, Western blot analysis demonstrated that saffron treatment induced changes in the expression of other key genes (DNMT1, DNMT3b, MBD2, CD44, HDAC3, c-Myc, NF-kB, TNFα, AR, N-RAS, and PTEN) in prostate cancer cells. Collectively, our findings demonstrate the important mechanisms by which saffron mediates anti-tumor properties in prostate cancer. These findings suggest that the use of saffron supplements alongside standard treatment protocols may yield beneficial effects for individuals with prostate cancer.


Assuntos
Produtos Biológicos , Crocus , Neoplasias da Próstata , Animais , Camundongos , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Próstata , Fator de Necrose Tumoral alfa , Administração Oral , Antígenos de Histocompatibilidade , Histona-Lisina N-Metiltransferase , Proteínas de Ligação a DNA
16.
Nutrients ; 14(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36014823

RESUMO

Intensive screening for better and safer medications to treat diseases such as cancer and inflammatory diseases continue, and some phytochemicals have been discovered to have anti-cancer and many therapeutical activities. Among the traditionally used spices, Crocus sativus (saffron) and its principal bioactive constituents have anti-inflammatory, antioxidant, and chemopreventive properties against multiple malignancies. Early reports have shown that the epigenetic profiles of healthy and tumor cells vary significantly in the context of different epigenetic factors. Multiple components, such as carotenoids as bioactive dietary phytochemicals, can directly or indirectly regulate epigenetic factors and alter gene expression profiles. Previous reports have shown the interaction between active saffron compounds with linker histone H1. Other reports have shown that high concentrations of saffron bind to the minor groove of calf thymus DNA, resulting in specific structural changes from B- to C-form of DNA. Moreover, the interaction of crocin G-quadruplex was reported. A recent in silico study has shown that residues of SIRT1 interact with saffron bio-active compounds and might enhance SIRT1 activation. Other reports have shown that the treatment of Saffron bio-active compounds increases γH2AX, decreases HDAC1 and phosphorylated histone H3 (p-H3). However, the question that still remains to be addressed how saffron triggers various epigenetic changes? Therefore, this review discusses the literature published till 2022 regarding saffron as dietary components and its impact on epigenetic mechanisms. Novel bioactive compounds such as saffron components that lead to epigenetic alterations might be a valuable strategy as an adjuvant therapeutic drug.


Assuntos
Crocus , Neoplasias , Crocus/química , DNA/química , Código das Histonas , Humanos , Compostos Fitoquímicos/química , Extratos Vegetais/química , Sirtuína 1
17.
World J Gastroenterol ; 28(25): 2782-2801, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35978869

RESUMO

Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer (CRC). While environmental factors and socio-economic realities of race remain predominant contributors to CRC disparities in African-Americans (AAs), this review focuses on the biological mediators of CRC disparity, namely the under-appreciated influence of inherited ancestral genetic regulation on mucosal innate immunity and its interaction with the microbiome. There remains a poor understanding of mechanisms linking immune-related genetic polymorphisms and microbiome diversity that could influence chronic inflammation and exacerbate CRC disparities in AAs. A better understanding of the relationship between host genetics, bacteria, and CRC pathogenesis will improve the prediction of cancer risk across race/ethnicity groups overall.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Negro ou Afro-Americano/genética , Neoplasias Colorretais/etiologia , Humanos , Inflamação/complicações , Inflamação/genética
18.
Front Pediatr ; 10: 886627, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35799697

RESUMO

Early infancy is critical for the development of an infant's gut flora. Many factors can influence microbiota development during the pre- and postnatal periods, including maternal factors, antibiotic exposure, mode of delivery, dietary patterns, and feeding type. Therefore, investigating the connection between these variables and host and microbiome interactions in neonatal development would be of great interest. As the "unculturable" era of microbiome research gives way to an intrinsically multidisciplinary field, microbiome research has reaped the advantages of technological advancements in next-generation sequencing, particularly 16S rRNA gene amplicon and shotgun sequencing, which have considerably expanded our knowledge about gut microbiota development during early life. Using omics approaches to explore the neonatal microbiome may help to better understand the link between the microbiome and newborn diseases. Herein, we summarized the metagenomics methods and tools used to advance knowledge on the neonatal microbiome origin and evolution and how the microbiome shapes early and late individuals' lives for health and disease. The way to overcome limitations in neonatal microbiome studies will be discussed.

19.
BMC Infect Dis ; 22(1): 552, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715729

RESUMO

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.


Assuntos
COVID-19 , Negro ou Afro-Americano , Idoso , Biomarcadores , Diarreia , Ferritinas , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina , Estudos Retrospectivos , SARS-CoV-2 , Troponina
20.
Res Sq ; 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35350203

RESUMO

Background: Coronavirus disease 2019 (COVID-19) and associated outcomes manifest differently depending on patients' background and pre-existing conditions. It remains unclear how African Americans with and without cancer have been affected. Aim: To determine epidemiological, clinical comorbidities, and laboratory test results to identify markers associated with mortality in COVID-19 cancer patients. Methods: We reviewed all Covid-19 hospitalized patients records from Dec. 2019 to Oct. 2021 at Howard University Hospital. Patients having a history of, or active cancer status were reviewed. All the clinical, treatment, lab values, and pathological data were extracted. Statical analysis of the Covid-19 cancer patients and comparison with non-cancer Covid-19 patients was performed using univariate and multivariate analyses. Results: Out of 512 COVID-19 infected patients, a total of 49 patients were identified with different types of cancer, with both active and previous history. Females consisted of 26 cancer patients (53%). African American race was predominant in both cases and controls, 83.6% and 66.7% respectively. Cancer patients were older than non-cancer patients (Mean Age-70.6 vs. 56.3 years) and had an increased length of hospital stay (Mean 13.9 vs 9.4 days). Among cancer patients, breast cancer was more prevalent in females and prostate cancer in males, (54% and 52% respectively). Comparison of patients with active vs. previous cancer showed no significant difference in the clinical outcome, death vs. discharge (P=0.34). A higher reduction in albumin level in cancer cases, from the time of admission to day five, was significantly associated with death during the same hospital stay compared to those discharged (n=24, 48.9%, p<0.001). In controls, Lymphopenia (n=436, 94.1%, p=0.05), AST (n=59, 12%, p=0.008) and Albumin (n=40, 10.7%, p=0.02) have shown an association with increased mortality. Conclusion: Albumin level has shown to have an inverse relationship with clinical outcomes among all COVID infected African American patients. Reduction in Albumin level during the hospital stay, particularly in COVID-19 cancer patients should be considered as a predictor of mortality. No significant difference was noticed in the clinical outcome in patients with previous versus active cancer. Further research with a large cohort size is needed to verify and identify other predictors of outcome in Covid-19 cancer patients and develop appropriate treatment modalities.

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