Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer.

Natural products have been a long-standing source for exploring health-beneficial components from time immemorial. Modern science has had a renewed interest in natural-products-based drug discovery. The quest for new potential secondary metabolites or exploring enhanced activities for existing molecules remains a pertinent topic for research. Resveratrol belongs to the stilbenoid polyphenols group that encompasses two phenol rings linked by ethylene bonds. Several plant species and foods, including grape skin and seeds, are the primary source of this compound. Resveratrol is known to possess potent anti-inflammatory, antiproliferative, and immunoregulatory properties. Among the notable bioactivities associated with resveratrol, its pivotal role in safeguarding the intestinal barrier is highlighted for its capacity to prevent intestinal inflammation and regulate the gut microbiome. A better understanding of how oxidative stress can be controlled using resveratrol and its capability to protect the intestinal barrier from a gut microbiome perspective can shed more light on associated physiological conditions. Additionally, resveratrol exhibits antitumor activity, proving its potential for cancer treatment and prevention. Moreover, cardioprotective, vasorelaxant, phytoestrogenic, and neuroprotective benefits have also been reported. The pharmaceutical industry continues to encounter difficulties administering resveratrol owing to its inadequate bioavailability and poor solubility, which must be addressed simultaneously. This report summarizes the currently available literature unveiling the pharmacological effects of resveratrol.

Synergistic Effects of Limosilactobacillus fermentum ASBT-2 with Oxyresveratrol Isolated from Coconut Shell Waste.

Value-added phytochemicals from food by-products and waste materials have gained much interest and among them, dietary polyphenolic compounds with potential biological properties extend a promising sustainable approach. Oxyresveratrol (Oxy), a stilbenoid polyphenol, possesses great therapeutic potential, though its pharmacokinetic issues need attention. A good source of oxyresveratrol was found in underutilized coconut shells and the synbiotic applications of the compound in combination with a potential probiotic isolate Limosilactobacillus fermentum ASBT-2 was investigated. The compound showed lower inhibitory effects on the strain with minimum inhibitory concentration (MIC) of 1000 µg/mL. Oxyresveratrol at sub-MIC concentrations (500 µg/mL and 250 µg/mL) enhanced the probiotic properties without exerting any inhibitory effects on the strain. The combination at sub- MIC concentration of the compound inhibited Salmonella enterica and in silico approaches were employed to elucidate the possible mode of action of oxy on the pathogen. Thus, the combination could target pathogens in the gut without exerting negative impacts on growth of beneficial strains. This approach could be a novel perspective to address the poor pharmacokinetic properties of the compound.

Pulmonary mucormycosis associated with medical marijuana use.

A 66-year-old man with diabetes presented to the hospital with a two-month history of dyspnea, cough, rust-colored sputum, night sweats and 20 pound weight loss. He had begun smoking medical marijuana 3 months earlier. CT of the chest showed multiple bilateral large ground glass opacities with surrounding consolidation. Infectious workup was negative. BAL was non-diagnostic. He was treated with broad spectrum antibiotics without improvement. VATS was performed and cultured lung tissue grew Rhizopus species. He was started on intravenous liposomal amphotericin B and micafungin and then transitioned to oral posaconazole after two weeks. Repeat CT two months later showed stable size of the cavities. One month later he died of massive pulmonary hemorrhage. Here we document what we believe is the first known case of pulmonary mucormycosis associated with medical marijuana use.

Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases.

BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Visceral leishmaniasis with associated immune dysregulation leading to lymphoma.

OBJECTIVE: We describe an atypical presentation of visceral leishmaniasis (VL) complicated by Epstein-Barr virus (EBV)-lymphoproliferative disorder and angioimmunoblastic T-cell lymphoma in a U.S. Government contractor recently deployed to Iraq and Afghanistan. METHODS: We performed a search of PubMed (1966-2012) using the terms visceral, leishmaniasis, operation, iraqi, freedom, desert, storm, EBV, lymphoproliferative, angioimmunoblastic, and lymphoma. The purpose of the search was two-fold: to find reported cases of VL during U.S. military operations and to ascertain if lymphoproliferative disorder (specifically, because of EBV) was ever described as a sequelae of VL. RESULTS: Case series of VL acquired in the Middle East between 1990 and 2012 showed that while fever, abdominal pain, and hepatosplenomegaly were common signs and symptoms of VL, diffuse lymphadenopathy (our patient's presentation) was rare. Moreover, VL in and of itself lends to profound immune dysregulation, leading to a myriad of complications to include EBV-lymphoproliferative diseases. CONCLUSIONS: Diffuse lymphadenopathy because of VL is a very atypical presentation for infection acquired in the Middle East. Clinicians must be mindful of the extreme immune dysfunction that occurs as a result of this potentially fatal infection and the associated complications to include EBV-related lymphoproliferative disorders and lymphoma.

Pneumonia in military trainees: a comparison study based on adenovirus serotype 14 infection.

BACKGROUND: Adenovirus serotype 14 (Ad-14) recently emerged as a respiratory pathogen in the United States, with studies suggesting higher morbidity and mortality. This study was conducted to determine whether Ad-14 is associated with clinical outcomes in otherwise healthy patients with pneumonia. METHODS: Medical records of military trainees hospitalized with pneumonia during an outbreak of Ad-14 infection were reviewed. Clinical, radiographic, and laboratory parameters were compared on the basis of Ad-14 infection. RESULTS: Two hundred thirty-four trainees received a diagnosis of pneumonia, and 83(35%) were hospitalized. Sixty-one percent of patients with pneumonia were Ad-14 positive; 43% of patients with Ad-14 pneumonia were hospitalized (83% of female patients and 40% of male patients; P = .04), compared with 40% of patients with Ad-14 negative cases. Ad-14 infection was associated with higher admission temperature (38.3°C [interquartile range, (IQR) 37.7, 39.4] vs 37.3°C [IQR (36.7, 38.5)]; P < .01) and lower white blood cell count (8.3 × 1000 cells/µL [IQR, 5.7, 12.4] vs 13 × 1000 cells/µL [IQR, 7.5, 12.9]; P = .01), neutrophil count (6.7 × 1000 cells/µL [IQR, 2.8, 9.7] vs 9.7 × 1000 cells/µL [IQR, 5.6, 12.1]; P = .02), lymphocyte count (0.9 × 1000 cells/µL [IQR, 0.8, 1.1] vs 1.3 × 1000 cells/µL [IQR, 1, 1.9]; P = .001), and platelet count (210 × 1000 cells/µL [IQR, 145, 285] vs 261 × 1000 cells/µL [IQR, 238, 343]; P < .01). Ad-14 pneumonia was not associated with specific radiographic findings, pneumonia severity score, intensive care unit admission, longer hospitalization, or 30-day mortality. CONCLUSIONS: During an outbreak of Ad-14 infection, Ad-14 infection was not associated with excess overall morbidity or mortality. Ad-14 infection was associated with specific laboratory and clinical parameters and higher hospitalization rates in female trainees. These data provide new insight to the epidemiology of Ad-14 infection.

Adenovirus serotype 14 pneumonia at a basic military training site in the United States, spring 2007: a case series.

Adenovirus, a frequent cause of mild respiratory disease in military trainees, can result in severe manifestations when outbreaks are caused by novel viral strains for which there is little pre-existing immunity. Twenty-five basic military trainees (BMTs) were hospitalized with adenovirus pneumonia from April 1, 2007 through June 21, 2007. Clinical findings for 9 of these patients with PCR-confirmed adenovirus serotype 14 were studied retrospectively. The clinical picture was characterized by cough (88.9%) and sputum production (77.8%). All trainees were febrile. Laboratory results showed 88.9% had normal white blood cell (WBC) counts, 66.7% with high monocytes, and 55.6% with low lymphocytes on differential. All had lobar pneumonia radiographically. One patient required the intensive care unit (ICU) and later expired. In conclusion, among hospitalized patients with the combination of fever, productive cough, normal WBC, a differential showing high monocytes and low lymphocytes in an immunocompetent young adult with lobar pneumonia warrants a high level of suspicion for adenovirus 14 pneumonia.