Modulatory effects of rutin and vitamin A on hyperglycemia induced glycation, oxidative stress and inflammation in high-fat-fructose diet animal model.

In the current study we investigated the impact of combination of rutin and vitamin A on glycated products, the glyoxalase system, oxidative markers, and inflammation in animals fed a high-fat high-fructose (HFFD) diet. Thirty rats were randomly divided into six groups (n = 5). The treatments, metformin (120 mg/kg), rutin (100 mg/kg), vitamin A (43 IU/kg), and a combination of rutin (100 mg/kg) and vitamin A (43 IU/kg) were given to relevant groups of rats along with high-fructose high-fat diet for 42 days. HbA1c, D-lactate, Glyoxylase-1, Hexokinase 2, malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT), nuclear transcription factor-B (NF-κB), interleukin-6 (IL-6), interleukin-8 (IL-8) and histological examinations were performed after 42 days. The docking simulations were conducted using Auto Dock package. The combined effects of rutin and vitamin A in treated rats significantly (p < 0.001) reduced HbA1c, hexokinase 2, and D-lactate levels while preventing cellular damage. The combination dramatically (p < 0.001) decreased MDA, CAT, and GPx in treated rats and decreased the expression of inflammatory cytokines such as IL-6 andIL-8, as well as the transcription factor NF-κB. The molecular docking investigations revealed that rutin had a strong affinity for several important biomolecules, including as NF-κB, Catalase, MDA, IL-6, hexokinase 2, and GPx. The results propose beneficial impact of rutin and vitamin A as a convincing treatment strategy to treat AGE-related disorders, such as diabetes, autism, alzheimer's, atherosclerosis.

Water Lung: An Interesting Case of Non-cardiogenic Pulmonary Edema in a Heart Failure Patient.

Contrast-induced pulmonary edema is a rare but life-threatening condition often missed in heart failure patients. We present a case of a 65-year-old female with a past medical history of coronary artery disease, diastolic heart failure, and chronic kidney disease who presented with chest pain. She received low osmolar intravenous (IV) contrast for cardiac catheterization. Within 24 hours of receiving the contrast, the patient developed respiratory distress, which was found to be secondary to pulmonary edema. Pulmonary edema was considered to be related to cardiogenic at first; however, the patient's physical examination was normal, with no jugular venous distention (JVD). A transthoracic echocardiogram showed a central venous pressure of 3 mmHg. The patient's respiratory condition improved after receiving an IV diuretic. Chart review showed that the patient had a similar presentation in the past, which was also thought to be related to heart failure leading to recurrent exposure to contrast. Non-cardiogenic pulmonary edema should be considered in the differential diagnosis of pulmonary edema in heart failure patients receiving contrast.

Nanoparticles Based Sensors for Cyanide Ion Sensing, Basic Principle, Mechanism and Applications.

Rapidly detecting potentially toxic ions such as cyanide is paramount to maintaining a sustainable and environmentally friendly ecosystem for living organisms. In recent years, molecular sensors have been developed to detect cyanide ions, which provide a naked-eye or fluorometric response, making them an ideal choice for cyanide sensing. Nanosensors, on the other hand, have become increasingly popular over the last two decades due water solubility, quick reaction times, environmental friendliness, and straightforward synthesis. Researchers have designed many nanosensors and successfully utilized them for the detection of cyanide ions in various environmental samples. The majority of these sensors use gold and silver-based nanosensors because cyanide ions have a high affinity for these metals ions and coordinate through covalent bonds. These metal nanoparticles are typically combined or coated with fluorescent materials, which quench their fluorescence. However, adding cyanide ions etches out the metal nanoparticles, restoring their fluorescence/color. This principle has been followed by most nanosensors used for cyanide ion sensing. In this review, different nanosensors and their sensing mechanisms are discussed in relation to cyanide ions. The primary purpose is to compare the sensing abilities of these sensors, mainly their sensitivity, advantages, application and to find out research gaps for future work. In this review paper, the development made in nanosensors in the last thirteen years (2010-2023) was discussed and the nanosensors for cyanide ions were compared with molecular sensors while the nanosensors with the excellent limit of detection were highlighted.

Food Application of Orange Seed Powder through Incorporation in Wheat Flour to Boost Vitamin and Mineral Profiles of Formulated Biscuits.

The significance of conducting research for its application has been noted as a result of the rising global food production and waste generation. As a result, there is increasing interest in fruits and vegetable seeds that contain bioactive chemicals, such as those that are obtained from orange seeds. In the current work, orange seed powder replaced wheat flour at 0, 2.5, 5, 7.5, and 10% levels, to observe changes in physicochemical features of developed biscuits. Proximate analysis of orange seed powder and wheat flour revealed that orange seed powder has high fat, fiber, protein, and ash contents as compared to wheat flour, whereas moisture contents in wheat flour were high. In developed biscuits, the highest values (percentage) of ash (9.68 ± 0.04), fiber (6.79 ± 0.12), protein (10.42 ± 0.25), and fat (36.90 ± 0.55) were found in biscuits developed with 10% orange seed powder. Orange seed powder was a comparatively good source of both macro and micro minerals, as compared to wheat flour. High contents of selenium (5.32 ± 0.03), iron (2.12 ± 0.05), zinc (3.88 ± 0.12), and manganese (2.25 ± 0.04) mg/100 g, present in orange seed powder, were the prominent findings of this research work, as wheat flours were observed to be deficient in these trace minerals. Contents of calcium, magnesium, potassium, zinc, manganese, zinc, and selenium in control biscuits were found 20.51 ± 0.08, 17.29 ± 0.04, 46.12 ± 0.05, 1.06 ± 0.01, 1.97 ± 0.01, 0.12 ± 0.01, and 0.11 ± 0.01 mg/100 g, respectively, and replacement of wheat flour with 10% orange seed powder increased values of these minerals to 103.90 ± 0.35, 44.35 ± 0.50, 71.29 ± 0.32, 2.59 ± 0.4, 2.75 ± 0.02, 1.31 ± 0.01, and 2.02 ± 0.05 mg/100 g, respectively. Vitamins E and K, which were not detected in wheat flour, were present in orange powder in high amount, whereas B group vitamins, which were also present in wheat flour, were observed in significantly high quantities in orange seed powder. Increment in vitamin A, D, E, K, and B complexes was significant as a result of orange seed powder supplementation, except for vitamins B1 and B2, which were slightly decreased. Sensory evaluation revealed that a 5% replacement of orange seed powder provided good quality biscuits with acceptable colour, flavor, taste, texture, and overall acceptability. Orange seed powder could prove an important ingredient in the baking industry with the potential of promoting the nutritional value of foods.

Systemically Administered Homing Peptide Targets Dystrophic Lesions and Delivers Transforming Growth Factor-ß (TGFß) Inhibitor to Attenuate Murine Muscular Dystrophy Pathology.

Muscular dystrophy is a progressively worsening and lethal disease, where accumulation of functionality-impairing fibrosis plays a key pathogenic role. Transforming growth factor-ß1 (TGFß1) is a central signaling molecule in the development of fibrosis in muscular dystrophic humans and mice. Inhibition of TGFß1 has proven beneficial in mouse models of muscular dystrophy, but the global strategies of TGFß1 inhibition produce significant detrimental side effects. Here, we investigated whether murine muscular dystrophy lesion-specific inhibition of TGFß1 signaling by the targeted delivery of therapeutic decorin (a natural TGFß inhibitor) by a vascular homing peptide CAR (CARSKNKDC) would reduce skeletal muscle fibrosis and pathology and increase functional characteristics of skeletal muscle. We demonstrate that CAR peptide homes to dystrophic lesions with specificity in two muscular dystrophy models. Recombinant fusion protein consisting of CAR peptide and decorin homes selectively to sites of skeletal muscle damage in mdxDBA2/J and gamma-sarcoglycan deficient DBA2/J mice. This targeted delivery reduced TGFß1 signaling as demonstrated by reduced nuclear pSMAD staining. Three weeks of targeted decorin treatment decreased both membrane permeability and fibrosis and improved skeletal muscle function in comparison to control treatments in the mdxD2 mice. These results show that selective delivery of decorin to the sites of skeletal muscle damage attenuates the progression of murine muscular dystrophy.

Standalone or combinatorial phenylbutyrate therapy shows excellent antiviral activity and mimics CREB3 silencing.

Herpesviruses are ubiquitous human pathogens that tightly regulate many cellular pathways including the unfolded protein response to endoplasmic reticulum (ER) stress. Pharmacological modulation of this pathway results in the inhibition of viral replication. In this study, we tested 4-phenylbutyrate (PBA), a chemical chaperone-based potent alleviator of ER stress, for its effects on herpes simplex virus (HSV) type 1 infection. Through in vitro studies, we observed that application of PBA to HSV-infected cells results in the down-regulation of a proviral, ER-localized host protein CREB3 and a resultant inhibition of viral protein synthesis. PBA treatment caused viral inhibition in cultured human corneas and human skin grafts as well as murine models of ocular and genital HSV infection. Thus, we propose that this drug can provide an alternative to current antivirals to treat both ocular HSV-1 and genital HSV-2 infections and may be a strong candidate for human trials.

The Status of Nutritional Management Guidelines for Head and Neck Cancer Patients.

Introduction Head and neck cancer (HNC) is the seventh leading cause of cancer worldwide. Approximately 35%-60% patients with HNC are malnourished from the disease onset, malnutrition being associated with worsened health outcomes among these patients. This study aimed to review and synthesize existing guidelines regarding nutritional interventions in HNC patients and assess providers' knowledge, opinions, and practice of guidelines for the nutritional management of HNC patients. Methods This is a multimethod study that includes a systematic review of guidelines for nutritional intervention in HNC patients and a providers' survey regarding their knowledge and opinions regarding nutrition therapy guidelines for HNC patients. Results Our review yielded seven guidelines. Of the seven guidelines reviewed, all were specific to cancer patients, however, only three were specific for HNC patients. Three of the guidelines recommended using a nutritional screening tool, however, only two mentioned a specific screening tool. Out of 193 surveys included in our analysis, the highest percentage of respondents were physicians (52.4%), followed by registered nurses (33.5%). The majority of respondent (77.5%) worked in a hospital-based practice, while 18.8% worked in clinic-based practice. A large proportion (46.6%) of respondents were not aware of nutritional guidelines for HNC patients; with 23.6% not aware of any, and 23.0% aware of their existence but not aware of their content. The majority (81.5%) of respondents said that a more detailed guideline should be available for HNC patient with regards to nutrition. Conclusion Nutritional deficiencies in HNC patients continue to cause significant complications in treatment and recovery. Existing practice guidelines are limited and lack specific recommendations. A universal standard of care with regard to addressing nutrition in HNC patients is needed to improve healthcare outcomes among NHC patients.

A Cross-Sectional Survey on Telemedicine Use for Doctor-Patient Communication.

Introduction Use of computers for doctor-patient communication is increasing. Considering effective doctor-patient communication is important for good health outcomes. This study helps to determine the level of acceptance of telemedicine in general public and factors associated with it. Methods: This survey with cross-sectional analysis comprised a brief survey with 15 questions. The survey was distributed in public places to determine the opinions of the general public. Results Randomly selected 125 participants completed the questionnaire. Synchronous telemedicine was favored by young people (82% in the 18-34 age group vs 37.5% of participants aged >55 years; p<0.01), those with a higher education level (46.7% of non-college-educated persons vs 80.6% of college-educated persons; p<0.01), and frequent computer users (67% who used a computer for less than two hours a month vs 86.5% of those who used a computer more than hours a month; p=0.03). Asynchronous communication, like sending health information to doctors via a safe portal was acknowledged mostly by people who had used patient portals in the past (84.1% vs 65.4%; p=0.02). Use of patient portals was less among older users and senior citizens (20.8% use in the age group >55 vs. 51.3% in the age group 35-53 years vs. 71% in age group 18-34 years). Receiving video education for specific health concerns was favored by those who used a computer frequently (94.6% who used a computer more than two hours a month vs 77% who used a computer less than two hours a month; p =0.02). Conclusion Telemedicine is generally favored, but physicians should be mindful about older people as they may not feel comfortable. Step by step guidance should be provided especially to senior citizens for telemedicine and portal use.

In Vitro and In Vivo Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection.

Herpes simplex virus type 2 (HSV-2) causes recurrent lesions in the anogenital area that may be transmitted through sexual encounters. Nucleoside analogs, such as acyclovir (ACV), are currently prescribed clinically to curb this infection. However, in some cases, reduced efficacy has been observed due to the emergence of resistance against these drugs. In our previous study, we reported the discovery of a novel anti-HSV-1 small molecule, BX795, which was originally used as an inhibitor of TANK-binding kinase 1 (TBK1). In this study, we report the antiviral efficacy of BX795 on HSV-2 infection in vaginal epithelial cells in vitro at 10 µM and in vivo at 50 µM. Additionally, through biochemical assays in vitro and histopathology in vivo, we show the tolerability of BX795 in vaginal epithelial cells at concentrations as high as 80 µM. Our investigations also revealed that the mechanism of action of BX795 antiviral activity stems from the reduction of viral protein translation via inhibition of protein kinase B phosphorylation. Finally, using a murine model of vaginal infection, we show that topical therapy using 50 µM BX795 is well tolerated and efficacious in controlling HSV-2 replication.

BX795 demonstrates potent antiviral benefits against herpes simplex Virus-1 infection of human cell lines.

Herpes simplex virus-1 (HSV-1) infection is known to cause skin blisters, keratitis as well as deadly cases of encephalitis in some situations. Only a few therapeutic modalities are available for this globally prevalent infection. Very recently, a small molecule BX795 was identified as an inhibitor of HSV-1 protein synthesis in an ocular model of infection. In order to demonstrate its broader antiviral benefits, this study was aimed at evaluating the antiviral efficacy, mode-of-action, and toxicity of BX795 against HSV-1 infection of three human cell lines: HeLa, HEK, and HCE. Several different assays, including cell survival analysis, imaging, plaque analysis, Immunoblotting, and qRT-PCR, were performed. In all cases, BX795 demonstrated low toxicity at therapeutic concentration and showed strong antiviral benefits. Quite interestingly, cell line-dependent differences in the mechanism of antiviral action and cytokine response to infection were seen upon BX795 treatment. Taken together, our results suggest that BX795 may exert its antiviral benefits via cell-line specific mechanisms.

Prior inhibition of AKT phosphorylation by BX795 can define a safer strategy to prevent herpes simplex virus-1 infection of the eye.

PURPOSE: To evaluate the prophylactic antiviral efficacy, corneal tolerance and toxicity of topically dosed BX795, a non-nucleoside small-molecule inhibitor of herpes simplex virus type-1 (HSV-1). METHODS: Prophylactic treatment with BX795 was performed both in-vitro on human corneal epithelial cells and in-vivo on mice prior to HSV-1 challenge. Viral burden was evaluated using a standard plaque assay. In a separate experiment, mice were treated topically 3-times daily for 4-weeks with BX795 to evaluate corneal tolerance and toxicity. Phenol-red thread measurements, fluorescein staining and optical coherence tomography (OCT) were used to evaluate tear production, dryness and corneal structural changes. Corneal sensitivity and intraocular pressure were measured using esthesiometery and tonometery respectively. RESULTS: Both in-vitro and in-vivo results showed a robust suppression of HSV-1 infection when treated prophylactically with BX795. The fluorescein stain and phenol-red results for the BX795-treated eyes did not show signs of corneal surface dryness when compared to trifluridine (TFT), an FDA-approved topical antiviral. The OCT measurements showed no signs of structural changes to the cornea suggesting that BX795 treatment was well tolerated without any apparent signs of toxicity or inflammation. The corneal sensitivity of BX795-treated eyes was not significantly different from TFT-treated eyes. No significant increase in the intraocular pressure of BX795-treated mice was observed. CONCLUSIONS: Prophylactic treatment with BX795 protects corneal cells from HSV-1 infection. The antiviral is well-tolerated on murine corneas without any detectable toxicity.

When the Heart Cries Wolf: Myocardial Bridging Presenting as Angina-like Chest Pain.

Myocardial bridging (MB) is the most common congenital coronary anomaly and refers to an intramural course of an epicardial coronary artery. The proximal segment of the left anterior descending artery (LAD) is the most commonly involved vessel and is often seen in patients with hypertrophic cardiomyopathy (HCM). We present a case of a 64-year-old female with left-sided non-exertional chest pain. Electrocardiography (EKG) and echocardiography were negative, however, stress EKG was positive with deep ST-segment depressions. Coronary angiography revealed mid-segment compression of LAD during systole, returning to its normal caliber during diastole. The patient remained asymptomatic during the hospital course and was later discharged on beta-blocker therapy. This case is different from others in a sense that it presented with severe pain like angina and mid-segment of LAD is involved rather than the proximal segment where it commonly occurs. This case report will help clinicians overcome the diagnostic challenge in patients presenting with atypical chest pain.

Correlation Between Vitamin D Deficiency and Diabetic Ketoacidosis.

Both type 1 and type 2 diabetes mellitus have been associated with vitamin D deficiency. Diabetic ketoacidosis, which is a complication of type 1 and, rarely, type 2 diabetes, is also found to be associated with vitamin D levels. This review discusses studies on the correlation between diabetic ketoacidosis and vitamin D levels. Studies show that vitamin D deficiency is associated with the occurrence of diabetic ketoacidosis. Diabetic ketoacidosis is also found to affect vitamin D levels. The possible explanation of diabetic ketoacidosis affecting vitamin D levels is the inactivity of the 1-alpha-hydroxylase enzyme and an increase in the renal excretion of vitamin D binding proteins. The presence of vitamin D receptors on pancreatic beta cells explains the role of vitamin D in the causation of diabetic ketoacidosis.

Dietary Habits and Physical Activity are Associated With the Risk of Breast Cancer Among Young Iranian Women: A Case-control Study on 1010 Premenopausal Women.

BACKGROUND: Several studies conducted in developed countries introduced diet and physical inactivity as major risk factors for several types of cancers. However, the impact of diet and physical inactivity on the risk of breast cancer (BC) is understudied, and the limited findings are controversial. In addition, no or limited knowledge is available from the developing world. PATIENTS AND METHODS: This case-control study was performed from November 2014 to March 2016 on 1010 young women aged 20 to 50 years who were newly diagnosed with BC. Data was obtained via a validated questionnaire and the global physical activity questionnaire (GPAQ2). Also, patients' medical and histopathology reports were reviewed. RESULTS: The results of multiple logistic regression suggested that, except for the common risk factors for BC (older marital age, family history of BC, smoking, and being a passive smoker), eating red meat (adjusted odds ratio [aOR] >8 portions/week [p/w] vs. 0-2 p/w, 1.15; 95% confidence interval [CI], 1.04-1.28); eating fish (aOR >8 p/w vs. 0-2 p/w, 1.55; 95% CI, 1.12-2.76), fruit consumption (aOR 0-4 p/w vs. >8 p/w, 1.96; 95% CI, 1.07-3.82), pickle consumption (aOR >8 p/w vs. 7-8 p/w, 1.46; 95% CI, 1.31-1.70), and intensity of physical activity (aOR light vs. vigorous, 1.68; 95% CI, 1.47-1.98) were directly associated with a higher risk of BC in young women. CONCLUSION: Our study supported the hypothesis that unhealthy dietary habits and physical inactivity are risk factors for BC. We found that a healthy diet containing low fat and high fruits and vegetables with regular exercise are effective ways to reduce the risk of BC among young women.