PMID: 

Int J Trichology. 2019 Mar-Apr;11(2):49-57. PMID: 31007473

Abstract Title: 

Serum Vitamin D Levels and Alopecia Areata- A Hospital Based Case-Control Study from North-India.

Abstract: 

Background: Alopecia areata (AA) is an autoimmune disease which is characterized by hair loss and affects any hair-bearing area. Low levels of Vitamin D have been implicated in a variety of autoimmune diseases. This study was conducted to assess the levels of Vitamin D in patients with AA and its correlation with severity, pattern, and extent of the disease.Materials and Methods: This hospital-based study included 135 cases with AA and 135 age- and sex-matched controls. AA cases were grouped according to the severity, pattern, and extent of the disease. The levels of Vitamin D were assessed and compared between cases and controls and among different groups of cases. The data were analyzed, and the correlation was derived.Results: The more number of patients from the case group had deficient and insufficient levels of Vitamin D as compared to controls, the difference being statistically significant (= 0.01). A highly significant difference was found in mean Vitamin D levels between cases and controls (= 0.0004). A negative correlation was found between Vitamin D levels and severity of AA as accessed by SALT score. A negative correlation was also found between Vitamin D levels with pattern and extent of the disease.Conclusion: Vitamin D deficiency may be one of the factors having a role either in etiopathogenesis or exacerbation of AA. Supplementation of Vitamin D as a treatment modality may improve the clinical outcome of AA.

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PMID: 

Skin Appendage Disord. 2019 Feb ;5(2):72-89. Epub 2018 Aug 21. PMID: 30815439

Abstract Title: 

Complementary and Alternative Treatments for Alopecia: A Comprehensive Review.

Abstract: 

The treatment of alopecia is limited by a lack of therapies that induce and sustain disease remission. Given the negative psychosocial impact of hair loss, patients that do not see significant hair restoration with conventional therapies often turn to complementary and alternative medicine (CAM). Although there are a variety of CAM treatment options on the market for alopecia, only a few are backed by multiple randomized controlled trials. Further, these modalities are not regulated by the Food and Drug Administration and there is a lack of standardization of bioactive in gredients in over-the-counter vitamins, herbs, and supplements. In this article, we provide a comprehensive review of the efficacy, safety, and tolerability of CAM, including natural products and mind and body practices, in the treatment of hair loss. Overall, there is a need for additional studies investigating CAM for alopecia with more robust clinical design and standardized, quantitative outcomes.

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PMID: 

Sci Rep. 2017 08 8 ;7(1):7529. Epub 2017 Aug 8. PMID: 28790339

Abstract Title: 

Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior.

Abstract: 

Although biopsies and tumor resection are prognostically beneficial for glioblastomas (GBM), potential negative effects have also been suggested. Here, using retrospective study of patients and intravital imaging of mice, we identify some of these negative aspects, including stimulation of proliferation and migration of non-resected tumor cells, and provide a strategy to prevent these adverse effects. By repeated high-resolution intravital microscopy, we show that biopsy-like injury in GBM induces migration and proliferation of tumor cells through chemokine (C-C motif) ligand 2 (CCL-2)-dependent recruitment of macrophages. Blocking macrophage recruitment or administrating dexamethasone, a commonly used glucocorticoid to prevent brain edema in GBM patients, suppressed the observed inflammatory response and subsequent tumor growth upon biopsy both in mice and in multifocal GBM patients. Taken together, our study suggests that inhibiting CCL-2-dependent recruitment of macrophages may further increase the clinical benefits from surgical and biopsy procedures.

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PMID: 

Breast Cancer Res. 2011 Aug 11 ;13(4):R78. Epub 2011 Aug 11. PMID: 21834963

Abstract Title: 

Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice.

Abstract: 

INTRODUCTION: High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice.METHODS: The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion.RESULTS: Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion.CONCLUSIONS: Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice.

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PMID: 

Nutrients. 2020 Feb 14 ;12(2). Epub 2020 Feb 14. PMID: 32075015

Abstract Title: 

Beneficial Effects of Dark Chocolate for Episodic Memory in Healthy Young Adults: A Parallel-Groups Acute Intervention with a White Chocolate Control.

Abstract: 

There is good evidence that cocoa flavonoids can acutely improve cognitive function in humans, possibly via mechanisms such as increased cerebral blood flow. To date, much of the evidence is based on measures of executive function with extracts and cocoa-based interventions with a high flavonoid content. The aim of the present study was to explore whether benefits to episodic verbal memory and mood are observed two hours post consumption of a commercially available dark chocolate (DC) bar relative to a 35 g white chocolate bar (WC). Ninety-eight healthy young adults (= 57 females) aged 18-24 years consumed either a 35 g DC bar or a calorie-matched low flavonoid WC bar. Verbal episodic memory and mood were assessed pre consumption and 2 h post consumption. An ANOVA analysis showed that the DC was associated with better verbal memory performance for several outcome measures of the Rey Auditory Verbal Learning Test relative to the WC, however, there were no effects on mood. These findings lend support to the notion that everyday available portions of dark chocolate can confer benefits to the brain in healthy consumers.

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PMID: 

Neoplasia. 2014 Nov ;16(11):950-60. Epub 2014 Nov 20. PMID: 25425969

Abstract Title: 

Core needle biopsy of breast cancer tumors increases distant metastases in a mouse model.

Abstract: 

INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome.METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice.RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group.CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases.

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PMID: 

Physiol Rep. 2018 04 ;6(8):e13679. PMID: 29687616

Abstract Title: 

Percutaneous muscle biopsy-induced tissue injury causes local endoplasmic reticulum stress.

Abstract: 

Endoplasmic reticulum (ER) stress is likely involved in the pathogenesis of metabolic dysfunction in people with obesity and diabetes. Although tissue biopsy is often used to evaluate the presence and severity of ER stress, it is not known whether acute tissue injury-induced by percutaneous muscle biopsy causes ER stress and its potential downstream effects on markers of inflammation and metabolic function. In this study, we tested the hypothesis that percutaneous biopsy-induced tissue injury causes ER stress and alters inflammatory and metabolic pathways in skeletal muscle. Vastus lateralis muscle tissue was obtained by percutaneous biopsy at 0600 h and 12 h later from either the contralateral leg (Group 1, n = 6) or at the same site as the initial biopsy (Group 2, n = 6) in women who were overweight. Muscle gene expression of selected markers of ER stress, inflammation, and regulators of glucose and lipid metabolism were determined. Compared with Group 1, muscle gene expression in the second biopsy sample obtained in Group 2 demonstrated marked increases in markers of ER stress (GRP78, XBP1, ATF6) and inflammation (IL6, TNF), and alterations in metabolic regulators (decreased expression of GLUT4 and PPARGC1A and increased expression of FASN). Our results suggest that acute tissue injury induced by percutaneous muscle biopsy causes an integrated local response that involves an induction of ER stress and alterations in markers of inflammation and regulators of glucose and lipid metabolism.

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PMID: 

Breast Cancer Res Treat. 2016 06 ;157(3):461-74. Epub 2016 Jun 1. PMID: 27249999

Abstract Title: 

Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation.

Abstract: 

Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to (1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, (2) characterize the type of inflammatory response present, and (3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e., immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy, and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore, biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human breast cancer. These findings may carry relevance in the clinical management of breast cancer.

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PMID: 

Breast Cancer Res Treat. 2013 Jun ;139(2):391-401. Epub 2013 May 29. PMID: 23715631

Abstract Title: 

Acute inflammation induced by the biopsy of mouse mammary tumors promotes the development of metastasis.

Abstract: 

Development of metastasis in peripheral tissues is a major problem in the fight to cure breast cancer. Although it is becoming evident that chronic inflammation can contribute to tumor progression and metastasis, the effect of acute inflammation in primary tumor is less known. Using mouse models for breast cancer here we show that biopsy of mammary tumors increases the frequency of lung metastases. This effect is associated with the recruitment of inflammatory cells to the lung and elevated levels of certain cytokines such as IL-6 in the lung airways. Antiinflammatory treatment prior to and after the biopsy reduces the development of metastases triggered by the biopsy. In addition, while lack of IL-6 does not affect primary tumor development, it protects from increasing number of metastases upon biopsy. Thus, our studies show that in addition to chronic inflammation, acute immune response caused by invasive procedures in the primary tumor may cause an increased risk on peripheral metastases, but the risk could be decreased by anti-inflammatory treatments.

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PMID: 

Circ Res. 2020 Feb 14. Epub 2020 Feb 14. PMID: 32078436

Abstract Title: 

Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The Cocoa-Pad Pilot Randomized Clinical Trial.

Abstract: 

Cocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity peripheral artery disease (PAD).In a phase II randomized clinical trial, to assess whether six months of cocoa improved walking performance in people with PAD, compared to placebo.Six-month double blind randomized clinical trial in which participants with PAD were randomized to either cocoa beverage vs. placebo beverage. The cocoa beverage contained 15 grams of cocoa and 75 mgs of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The two primary outcomes were six-month change in six-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A one-sided P value

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