Vibrational spectroscopy identifies myocardial chemical modifications in heart failure with preserved ejection fraction.

BACKGROUND: Vibrational spectroscopy can be a valuable tool to monitor the markers of cardiovascular diseases. In the present work, we explored the vibrational spectroscopy characteristics of the cardiac tissue in an experimental model of heart failure with preserved ejection fraction (HFpEF). The goal was to detect early cardiac chemical modifications associated with the development of HFpEF. METHODS: We used the Fourier-transform infrared (FTIR) and Raman micro-spectroscopic techniques to provide complementary and objective tools for the histological assessment of heart tissues from an animal model of HFpEF. A new sampling technique was adopted (tissue print on a CaF2 disk) to characterize the extracellular matrix. RESULTS: Several spectroscopic markers (lipids, carbohydrates, and glutamate bands) were recognized in the cardiac ventricles due to the comorbidities associated with the pathology, such as obesity and diabetes. Besides, abnormal collagen cross-linking and a decrease in tryptophan content were observed and related to the stiffening of ventricles and to the inflammatory state which is a favourable condition for HFpEF. CONCLUSIONS: By the analyses of tissues and tissue prints, FTIR and Raman techniques were shown to be highly sensitive and selective in detecting changes in the chemistry of the heart in experimental HFpEF and its related comorbidities. Vibrational spectroscopy is a new approach that can identify novel biomarkers for early detection of HFpEF.

FTIR Analysis of Renal Tissue for the Assessment of Hypertensive Organ Damage and proANP31-67 Treatment.

The kidneys are one of the main end organs targeted by hypertensive disease. Although the central role of the kidneys in the regulation of high blood pressure has been long recognized, the detailed mechanisms behind the pathophysiology of renal damage in hypertension remain a matter of investigation. Early renal biochemical alterations due to salt-induced hypertension in Dahl/salt-sensitive rats were monitored by Fourier-Transform Infrared (FTIR) micro-imaging. Furthermore, FTIR was used to investigate the effects of proANP31-67, a linear fragment of pro-atrial natriuretic peptide, on the renal tissue of hypertensive rats. Different hypertension-induced alterations were detected in the renal parenchyma and blood vessels by the combination of FTIR imaging and principal component analysis on specific spectral regions. Changes in amino acids and protein contents observed in renal blood vessels were independent of altered lipid, carbohydrate, and glycoprotein contents in the renal parenchyma. FTIR micro-imaging was found to be a reliable tool for monitoring the remarkable heterogeneity of kidney tissue and its hypertension-induced alterations. In addition, FTIR detected a significant reduction in these hypertension-induced alterations in the kidneys of proANP31-67-treated rats, further indicating the high sensitivity of this cutting-edge imaging modality and the beneficial effects of this novel medication on the kidneys.

Diagnostic accuracy of circular RNA for diabetes Mellitus: a systematic review and diagnostic Meta-analysis.

BACKGROUND: This study aimed to investigate the pooled diagnostic ability of circular RNA (circRNA) molecules for diabetes mellitus. METHODS: We searched PubMed, Scopus, and Web of Science for relevant studies. A total of 2070 participants, including 775 diabetic patients and 1295 healthy individuals, from five studies were included in this meta-analysis. True positive, true negative, false positive, and false negative data were extracted to calculate pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristics curve. The Deeks' funnel plot was applied for publication bias assessment, Cochran's Q test and I2 index were applied for inter-study heterogeneity assessment. Besides, a subgroup analysis was performed for determining the source of heterogeneity between studies. P value < 0.05 was considered significance. All analysis were done by STATA version 14. RESULTS: CircRNA presented a sensitivity of 76% (95% confidence interval [95%CI]: 66-84%), specificity of 77% (95%CI: 58-89%), positive LR of 3.25 (95%CI: 1.69-6.23), negative LR of 0.31 (95%CI: 0.21-0.46), DOR of 10.41 (95%CI: 4.26-25.41), and AUC of 0.82 (95%CI: 0.79-0.85) for diabetes mellitus detection. More specifically, hsa_circ_0054633 showed a sensitivity of 67% (95%CI: 53-81%) and a specificity of 82% (95%CI: 63-100%). CONCLUSION: CircRNAs show highly accurate diagnostic capability for type 2 diabetes mellitus and gestational diabetes mellitus. High sensitivity of circRNAs introduces them as potential noninvasive biomarkers for early diagnosis of diabetes mellitus and their high specificity introduces them as potential therapeutic targets by regulation of their expression.

Diagnostic performance of microRNAs in the detection of heart failure with reduced or preserved ejection fraction: a systematic review and meta-analysis.

AIM: Chronic heart failure (CHF) can be classified as heart failure with preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF). Currently, there is an unmet need for a minimally invasive diagnostic tool for different forms of CHF. We aimed to investigate the diagnostic potential of circulating microRNAs (miRNAs) for the detection of different CHF forms via a systematic review and meta-analysis approach. METHODS AND RESULTS: Comprehensive search on Medline, Web of Science, Scopus, and EMBASE identified 45 relevant studies which were used for qualitative assessment. Out of these, 29 studies were used for qualitative and quantitative assessment and allowed to identify a miRNA panel able to detect HFrEF and HFpEF with areas under the curve (AUC) of 0.86 and 0.79, respectively. A panel of eight miRNAs (hsa-miR-18b-3p, hsa-miR-21-5p, hsa-miR-22-3p, hsa-miR-92b-3p, hsa-miR-129-5p, hsa-miR-320a-5p, hsa-miR-423-5p, and hsa-miR-675-5p) detected HFrEF cases with a sensitivity of 0.85, specificity of 0.88 and AUC of 0.91. A panel of seven miRNAs (hsa-miR-19b-3p, hsa-miR-30c-5p, hsa-miR-206, hsa-miR-221-3p, hsa-miR-328-5p, hsa-miR-375-3p, and hsa-miR-424-5p) identified HFpEF cases with a sensitivity of 0.82 and a specificity of 0.61. CONCLUSIONS: Although conventional biomarkers (N-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide) presented a better performance in detecting CHF patients, the results presented here pointed towards specific miRNA panels with potential additive values to circulating natriuretic peptides in the diagnosis of different classes of CHF. Equally important, miRNAs alone showed a reasonable capacity for 'ruling out' patients with HFrEF or HFpEF. Additional studies with large populations are required to confirm the diagnostic potential of miRNAs for sub-classes of CHF.

A retrospective study comparing oral health in cancer patients and healthy people.

The purpose of this study was to investigate the relationship between oral and dental health in cancer patients and control group, which was conducted in Tabriz Shahid Gazi hospital. A researchers-made and validated questionnaire including oral and dental health criteria, was filled by the cancer patients (201 cases) and healthy controls (199 cases). Then, the results of the study were analyzed by SPSS software, and reported as Odds ratios (95 % confidence intervals) in tow groups. The results indicate that comparison of filled tooth, tooth extraction, dental caries, and gingival problems including bleeding, gum surgery and inflammation in cancer and controls were significantly meaningful. However, the comparison between the two groups was not significant in terms of the type of the tooth (natural or denture) and the number of daily toothbrushes, but they were considered as risk factors due to statistical results. Environmental factors, and especially oral hygiene, can play an important role in the incidence of different cancers. Among these, the type of oral microorganisms, and their overgrowth and released antigens should be studied further in the emergence of different kinds of cancer in humans.

PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD).

Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLR expression is adjusted at the transcriptional level through sterol regulatory element binding protein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and the inducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing the concentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, the effect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 have been proposed which concentrate on both extracellular and intracellular PCSK9, and they include blockage of PCSK9 production by using gene silencing agents and blockage of it's binding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tiny molecule inhibitors.

Purification of hyaluronidase as an anticancer agent inhibiting CD44.

Hyaluronidase (Hyal) can be employed to accomplish a diversity of complications related to hyaluronic acid (HA). Hyal contains some classes of catalysts that cleave HA. This enzyme is detected in several human tissues as well as in animal venoms, pathogenic organisms and cancers. Destructive cancer cells regularly increase the CD44 receptor existing in a cell membrane. This receptor acts as an exact receptor for HA, and HA is recognized to motivate the migration, spread, attack and metastasis of cancer cells. Nearly all of the methods used to purify Hyal are highly costly and not proper for industrial applications. This survey aims to review different methods of Hyal purification, which acts as an anticancer agent by degrading HA in tissues and thus inhibiting the CD44-HA interaction. Hyal can be successfully employed in the management of cancer, which is associated with HA-CD44. This review has described different methods for Hyal purification to prepare an origin to develop a novel purification technique for this highly appreciated protein. Using multiple columns is not applicable for the purification of Hyal and thus cannot be used at the industrial level. It is better to use affinity chromatography of anti-Hyal for Hyal with one-step purification.

Apelin, a promising target for Alzheimer disease prevention and treatment.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with high outbreak rates. It is estimated that about 35 million individuals around the world suffered from dementia in 2010. AD is expected to increase twofold every 20 years and, by 2030, approximately 65 million people could suffer from this illness. AD is determined clinically by a cognitive impairment and pathologically by the production of amyloid beta (Aß), neurofibrillary tangles, toxic free radicals and inflammatory mediators in the brain. There is still no treatment to cure or even alter the progressive course of this disease; however, many new therapies are being investigated and are at various stages of clinical trials. Neuropeptides are signaling molecules used by neurons to communicate with each other. One of the important neuropeptides is apelin, which can be isolated from bovine stomach. Apelin and its receptor APJ have been shown to broadly disseminate in the neurons and oligodendrocytes of the central nervous system. Apelin-13 is known to be the predominant neuropeptide in neuroprotection. It is involved in the processes of memory and learning as well as the prevention of neuronal damage. Studies have shown that apelin can directly or indirectly prevent the production of Aß and reduce its amounts by increasing its degradation. Phosphorylation and accumulation of tau protein may also be inhibited by apelin. Apelin is considered as an anti-inflammatory agent by preventing the production of inflammatory mediators such as interleukin-1ß and tumor necrosis factor alpha. It has been shown that in vivo and in vitro anti-apoptotic effects of apelin have prevented the death of neurons. In this review, we describe the various functions of apelin associated with AD and present an integrated overview of recent findings that, in general, recommend apelin as a promising therapeutic agent in the treatment of this ailment.

Purification and Characterization of Bovine Serum Albumin Using Chromatographic Method.

Purpose: Albumin is an abundant protein of blood and has many biopharmaceutical applications. The aim of this study was to purify bovine serum albumin (BSA) using produced rabbit anti-BSA antibody. Methods: The polyclonal antibody was produced against the BSA in rabbits. Then, the pure BSA was injected to three white New Zealand rabbits. ELISA test was done to evaluate antibody production. After antibody purification,the purified antibody was attached to CNBr-activated sepharose and finally it was used for purification of albumin from bovine serum. Western blotting analysis was used for functional assessment of immunoaffinity purified BSA. Results: The titer of anti-bovine albumin determined by ELISA was obtained 1: 256000. The SDS-PAGE showed up to 98% purity of isolated BSA and western blotting confirmed the BSA functionality. Purified bovine serum albumin by affinity chromatography showed a single band with molecular weight of 66 KDa. Conclusion: Affinity chromatography using produced rabbit anti-BSA antibody would be an economical and safe method for purification of BSA.