Publications by authors named "Thozhukat Sathyapalan"

225 Publications

Anti-proliferative potential of fluorinated curcumin analogues: experimental and computational analysis and review of the literature.

Curr Med Chem 2021 Sep 10. Epub 2021 Sep 10.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad. Iran.

Background: Curcuminoids, flavoring, and coloring agents in food have potent antioxidant, anti-tumor activity, and anti-inflammatory effects. However, they are rapidly metabolized to lesser active metabolites. Therefore, various studies have been conducted to synthesize new and stable curcumin analogues with enhanced therapeutic activity.

Methods: Fluorinated curcumin compounds (2a-2f) were synthesized by Knoevenagel condensation between fluorobenzaldehydes (1a-1f) with curcumin. Fluorinated demethoxycurcumin (3a) was synthesized by condensation between demethoxycurcumin and 3,4-difluorobenzaldehyde (1f). The structures of these compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR, 19FNMR, and mass spectroscopy. Antiproliferative activities of these synthetic compounds were evaluated against breast cancer cells (4T1), melanoma cancer cells (B16F10), and normal cell lines (NIH 3T3) using MTT assay. The interaction of curcumin, 2f and 3a with several proteins (1HCL, 2ZOQ, 3D94, 5EW3, 4WA9, 1XKK, 6CCY) was investigated. The structural preservation of the epidermal growth factor receptor (EGFR) was investigated by molecular dynamics simulation.

Results: The spectroscopic data obtained confirmed the proposed structure of fluorinated analogues. The results showed that compounds 2f and 3a inhibited cancer cells proliferation significantly more than other compounds. Compounds 2f and 3a showed the highest affinity and lowest binding energy with EGFR. The binding energies were -7.8, -10, and -9.8 kcal/mol for curcumin, 2f and 3a with EGFR, respectively. The molecular docking results demonstrated that compounds 2f and 3a were firmly bound in a complex with EGFR via the formation of a hydrogen bond.

Conclusion: In summary, we found that fluorinated demethoxycurcumin and fluorinated curcumin induces cancer cell death and binds to EGFR with high affinity.
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http://dx.doi.org/10.2174/0929867328666210910141316DOI Listing
September 2021

The Effect of Statins on C-Reactive Protein in Stroke Patients: A Systematic Review of Clinical Trials.

Mediators Inflamm 2021 27;2021:7104934. Epub 2021 Aug 27.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Statins reportedly have anti-inflammatory effects aside from their lipid-lowering impact. We investigated the effects of statin therapy on the level of C-reactive protein (CRP) or highly sensitive CRP (hs-CRP), a liver-derived marker of systemic inflammation, among stroke patients.

Methods: An online search was performed in Scopus, PubMed/MEDLINE, ISI Web of Science, and Google Scholar up to November 2020 to recognize clinical trials investigating the effects of statins on the CRP level in stroke patients.

Results: Overall, nine studies (11 treatment arms) with 1659 participants met the inclusion criteria. Six out of 9 studies (8 out of 11 arms) were categorized as studies with a high-quality methodological approach using the Cochrane Collaboration's tool. Data from 5 treatment arms indicated a significant decrease in CRP concentration, and in one treatment arm, CRP concentration did not suggest any considerable alteration following statin therapy. Moreover, two treatment arms showed a significant reduction in hs-CRP concentration and three treatment arms revealed no significant alteration in hs-CRP concentration following statin therapy. Generally, results were heterogeneous and independent of the type of statin, statin dose, treatment duration, and changes in plasma low-density lipoprotein cholesterol concentration.

Conclusion: The results suggest that statin therapy could reduce and, therefore, could be considered in these patients as potential anti-inflammatory agents.
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http://dx.doi.org/10.1155/2021/7104934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418548PMC
August 2021

Effect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trials.

Phytother Res 2021 Sep 2. Epub 2021 Sep 2.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = -0.40 mg/L; 95% CI: -0.70 to -0.09 mg/L; p = .01) and CRP (MWD = -0.31 mg/L; 95% CI: -0.47 to -0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = -0.48 mg/L; 95% CI: -0.92 to -0.04 mg/L; p = .03) and CRP (WMD = -0.47 mg/L, 95% CI = -0.69 to -0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day.
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http://dx.doi.org/10.1002/ptr.7262DOI Listing
September 2021

Refractory hypokalaemia and hypertension with metabolic alkalosis: an acute presentation of Cushing's disease secondary to a pituitary macroadenoma.

BMJ Case Rep 2021 Aug 26;14(8). Epub 2021 Aug 26.

Diabetes and Endocrinology, Hull University Teaching Hospitals NHS Trust, Hull, UK.

A 68-year-old woman presented with right arm cellulitis, not responsive to oral antibiotics. Intravenous antibiotics were commenced, and an ultrasound scan confirmed a collection that was surgically drained. She developed refractory hypokalaemia with normal magnesium, no gastrointestinal losses and no iatrogenic cause. She was hypertensive, hyperglycaemic, alkalotic, clinically obese with proximal myopathy and skin bruising. These clinical findings and refractory hypokalaemic hypertension with metabolic alkalosis raised a suspicion of Cushing's syndrome (CS). 24-hour urinary free cortisol (24 hours) was grossly raised on two occasions. The adrenocorticotropic hormone (ACTH) was significantly raised at 154 ng/L, confirming ACTH-dependant CS. A CT scan of the thorax, abdomen and pelvis excluded an ectopic source of hypercortisolaemia. MRI pituitary revealed an invasive macroadenoma. Treatment with endoscopic debulking resulted in the resolution of hypokalaemia and metabolic alkalosis with significant improvement in hyperglycaemia and hypertension.
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http://dx.doi.org/10.1136/bcr-2021-244850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395277PMC
August 2021

PLGA-Based Curcumin Delivery System: An Interesting Therapeutic Approach in Treatment of Alzheimer's Disease.

Curr Neuropharmacol 2021 Aug 22. Epub 2021 Aug 22.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad. Iran.

Progressive degeneration and dysfunction of the nervous system because of oxidative stress, aggregations of misfolded proteins, and neuroinflammation are the key pathological features of neurodegenerative diseases. Alzheimer's disease is a chronic neurodegenerative disorder driven by uncontrolled extracellular deposition of β-amyloid (Aβ) in the amyloid plaques and intracellular accumulation of hyperphosphorylated tau protein. Curcumin is a hydrophobic polyphenol with noticeable neuroprotective and anti-inflammatory effects that can cross the blood-brain barrier. Therefore, it is widely studied for the alleviation of inflammatory and neurological disorders. However, the clinical application of curcumin is limited due to its low aqueous solubility and bioavailability. Recently, nano-based curcumin delivery systems are developed to overcome these limitations effectively. This review article discusses the effects and potential mechanisms of curcumin-loaded PLGA nanoparticles in Alzheimer's disease.
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http://dx.doi.org/10.2174/1570159X19666210823103020DOI Listing
August 2021

Impact of severe hypoglycemia on the heat shock and related protein response.

Sci Rep 2021 Aug 23;11(1):17057. Epub 2021 Aug 23.

Royal College of Surgeons of Ireland, PO Box 15503, Adliya, Bahrain.

Heat shock proteins contribute to diabetes-induced complications and are affected by glycemic control. Our hypothesis was that hypoglycemia-induced heat shock and related protein changes would be amplified in type 2 diabetes (T2D). This prospective, case-control study enrolled 23 T2D patients and 23 control subjects who underwent hyperinsulinemic-induced hypoglycemia (≤ 2.0 mmol/L (36 mg/dl)) with blood sampling at baseline, at hypoglycemia and after a 24-h post-hypoglycemia follow-up period. Proteomic analysis of heat shock-related and pro-inflammatory proteins was performed. At baseline, MAPKAPK5 (p = 0.02) and UBE2G2 (p = 0.003) were elevated and STUB1 decreased (p = 0.007) in T2D. At hypoglycemia: PPP3CA (p < 0.03) was increased and EPHA2 (p = 0.01) reduced in T2D; by contrast, three proteins were reduced in controls [HSPA1A (p = 0.007), HSPB1 (p < 0.02), SMAD3 (p = 0.005)] while only MAPKAPK5 was elevated (p = 0.02). In the post-hypoglycemia follow-up period, most proteins normalized to baseline by 24-h; however, STIP1 (p = 0.003), UBE2N (p = 0.004) and UBE2L3 (p < 0.04) were decreased in controls at 24-h. No protein differed from baseline at 24-h in T2D. Pro-inflammatory interleukin-6 increased at 4-h post-hypoglycemia in controls and T2D (p < 0.05 and p < 0.003, respectively) and correlated with HSPA1A; anti-inflammatory IL-10 decreased 2-h post-hypoglycemia in T2D only. Other pro-inflammatory proteins, IL-1α, IFN-γ and TNF-α, were unchanged. Heat shock and related proteins differed at baseline between T2D and controls, with an exaggerated response of heat shock and related proteins to hypoglycemia that returned to baseline, though with changes at 24-h in controls alone. An increase in pro-inflammatory IL-6, with a decrease in anti-inflammatory IL-10, suggests that the HSP system is overactivated due to underlying inflammation in T2D.Trial registration: ClinicalTrials.gov NCT03102801.
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http://dx.doi.org/10.1038/s41598-021-96642-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382834PMC
August 2021

Recent advances in lung cancer therapy based on nanomaterials: a review.

Curr Med Chem 2021 Aug 10. Epub 2021 Aug 10.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.

Lung cancer is one of the commonest cancers with a significant mortality rate for both genders, particularly in men. Lung cancer is recognized as one of the leading cause of death worldwide, which threatens the lives of over 1.6 million people every day.. Although cancer is the leading cause of death in industrialized countries, conventional anticancer medications are unlikely to increase patients' life expectancy and quality of life significantly. In recent years, there are significant advances in the development and application of nanotechnology in cancer treatment. The superiority of nanostructured approaches is that they act more selectively than traditional agents. This progress led to the development of a novel field of cancer treatment known as nanomedicine. Various formulations based on nanocarriers, including lipids, polymers, liposomes, nanoparticles and dendrimers have opened new horizons in lung cancer therapy. The application and expansion of nano-agents lead to an exciting and challenging research era in pharmaceutical science, especially for the delivery of emerging anti-cancer agents. The objective of this review is to discuss the recent advances in three types of nanoparticle formulations for lung cancer treatments modalities including liposomes, polymeric micelles, and dendrimers for efficient drug delivery. Afterward, we have summarized the promising clinical data on nanomaterials based therapeutic apperoches in ongoing clinical studies.
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http://dx.doi.org/10.2174/0929867328666210810160901DOI Listing
August 2021

Implications on the Therapeutic Potential of Statins Modulation of Autophagy.

Oxid Med Cell Longev 2021 30;2021:9599608. Epub 2021 Jul 30.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Statins, which are functionally known as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) inhibitors, are lipid-lowering compounds widely prescribed in patients with cardiovascular diseases (CVD). Several biological and therapeutic functions have been attributed to statins, including neuroprotection, antioxidation, anti-inflammation, and anticancer effects. Pharmacological characteristics of statins have been attributed to their involvement in the modulation of several cellular signaling pathways. Over the past few years, the therapeutic role of statins has partially been attributed to the induction of autophagy, which is critical in maintaining cellular homeostasis and accounts for the removal of unfavorable cells or specific organelles within cells. Dysregulated mechanisms of the autophagy pathway have been attributed to the etiopathogenesis of various disorders, including neurodegenerative disorders, malignancies, infections, and even aging. Autophagy functions as a double-edged sword during tumor metastasis. On the one hand, it plays a role in inhibiting metastasis through restricting necrosis of tumor cells, suppressing the infiltration of the inflammatory cell to the tumor niche, and generating the release of mediators that induce potent immune responses against tumor cells. On the other hand, autophagy has also been associated with promoting tumor metastasis. Several anticancer medications which are aimed at inducing autophagy in the tumor cells are related to statins. This review article discusses the implications of statins in the induction of autophagy and, hence, the treatment of various disorders.
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http://dx.doi.org/10.1155/2021/9599608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349293PMC
July 2021

Curcumin for the Treatment of Prostate Diseases: A Systematic Review of Controlled Clinical Trials.

Adv Exp Med Biol 2021 ;1291:345-362

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Prostate cancer is one of the significant causes of morbidity and mortality worldwide. Benign prostatic hyperplasia is another condition of the prostate which, like prostate cancer, is more common among ageing men and is linked to inflammation. In this study, a systematic review was undertaken to estimate the effect of turmeric or curcumin supplementation on prostate diseases. A comprehensive search was conducted in PubMed, Scopus, ISI Web of Science and Google Scholar up to 15 April 2020 to identify clinical trials assessing the effects of curcumin/turmeric alone or in combination with other herbs on prostate diseases. This led to the identification of 11 records comprising 745 patients who met the eligibility criteria. Eight studies were conducted on patients with prostate cancer, and three were on other diseases of the prostate. Although outcomes across the studies were heterogeneous, in some studies curcumin/turmeric supplementation had some favourable effects. This included beneficial effects on the levels of prostate-specific antigen (PSA) (2/6 studies), quality of life (1/2 studies), as well as on oxidative stress markers, feelings of incomplete bladder emptying, urination frequency, intermittency, urgency, weak stream, straining and nocturia. Curcumin/turmeric supplementation had no significant adverse effects among patients. This study demonstrated that turmeric or curcumin supplementation might have beneficial effects on some parameters related to prostate diseases, but it should be noted that some studies showed no effect. Therefore, further studies using curcumin-related compounds, particularly in highly bioavailable forms, are needed to assess the impact of curcumin on prostate conditions.
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http://dx.doi.org/10.1007/978-3-030-56153-6_20DOI Listing
August 2021

The Use of Curcumin for the Treatment of Renal Disorders: A Systematic Review of Randomized Controlled Trials.

Adv Exp Med Biol 2021 ;1291:327-343

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Chronic kidney disease (CKD) is one of the significant causes of morbidity and mortality worldwide, which could develop and progress to end-stage renal disease. Increased inflammation and reduced antioxidant capacity commonly occur in CKD and hemodialysis patients. Curcumin is a natural bioactive compound with antioxidant and anti-inflammatory properties. This systematic review was undertaken with the main aim of assessing the effects of curcumin/turmeric supplementation on renal diseases based on clinical trials. A comprehensive search was performed in PubMed/MEDLINE, Scopus, ISI Web of Science, and Google Scholar from inception up to April 6, 2020 to identify clinical trials assessing the effects of curcumin or turmeric alone, or in combination with other herbs or nutrients on renal diseases. Twelve studies met the eligibility criteria. These randomized controlled trials (RCTs) comprised 631 patients with either chronic kidney diseases (CKD), hemodialysis, diabetic proteinuria and nephropathy, and lupus nephritis. Curcumin/turmeric supplementation had favorable effects on renal diseases, particularly in terms of inflammation and oxidative stress. However, with the exception for proteinuria, their impact on clinical parameters, such as blood urea nitrogen, creatinine, glomerular filtration rate (GFR), and serum albumin, was weak and not significant. No serious adverse effects were reported following curcumin/turmeric supplementation. Within the limitations of this review, it can be concluded that curcumin/turmeric supplementation might have some beneficial effects on inflammatory and oxidative stress parameters of patients but no considerable positive impact on clinical outcomes of kidney diseases, apart from proteinuria.
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http://dx.doi.org/10.1007/978-3-030-56153-6_19DOI Listing
August 2021

A Systematic Review of the Clinical Use of Curcumin for the Treatment of Osteoarthritis.

Adv Exp Med Biol 2021 ;1291:265-282

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Osteoarthritis is characterized by degeneration of joint structure over time, resulting in limitation of joint mobility. There is growing evidence that curcumin has anti-inflammatory properties and could be a potential therapeutic option for chronic inflammatory diseases. Hence, curcumin could potentially have a positive impact on osteoarthritis symptoms. This systematic review aimed to estimate the effects of curcumin on osteoarthritis. We systematically searched PubMed, ISI, Scopus, and Google Scholar up to March 4, 2020 to identify randomized controlled trials that evaluated the effects of consumption of all types of curcumin compounds in the treatment of osteoarthritis, especially in patients with knee osteoarthritis. Seventeen trials were identified. The duration of the included studies varied from 4 weeks to 8 months. Across all trials, 13 studies involved screening using Western Ontario and McMaster Universities (WOMAC) scores and 11 studies used visual analog scales (VAS) for recording pain from baseline to post-intervention. There was a significant improvement in VAS and overall WOMAC scores with oral administration of various types of curcumin formulations with no severe adverse effects. In conclusion, different types of curcumin compounds may be beneficial as an alternative or complementary agent for the management of osteoarthritis. Moreover, certain curcumin compounds with higher bioavailability tended to show more positive effects.
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http://dx.doi.org/10.1007/978-3-030-56153-6_16DOI Listing
August 2021

The Clinical Use of Curcumin for the Treatment of Rheumatoid Arthritis: A Systematic Review of Clinical Trials.

Adv Exp Med Biol 2021 ;1291:251-263

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, which is prevalent in about 0.5-1.0% of the world population. Newer therapies for RA have only minimal efficacy in some cases and some adverse effects. Curcumin with anti-antioxidant, anti-inflammatory, and immunomodulatory properties might have beneficial effects on RA. We have carried out a systematic review with the main aim of estimating the effect of curcumin supplementation on RA. A systematic search of the medical databases, PubMed, Scopus, ISI, and Google Scholar was performed up to March 21, 2020 to identify clinical trials assessing the effect of turmeric or curcumin on RA. Six studies, comprising 259 patients with RA of 6-12 weeks duration, were included. Disease activity was assessed using 28 joints (DAS-28), visual analog scale (VAS), and American College of Rheumatology (ACR-20) scores. Treatment with curcumin significantly reduced DAS-28 scores in four out of five studies and VAS scores for pain in all three studies and significantly increased ACR-20 scores in all three studies in which it was measured. Erythrocyte sedimentation rate (ESR) and circulating C-reactive protein (CRP) were assessed in six and five studies, respectively, out of which four studies reported significant reductions in these parameters in response to curcumin treatment. Rheumatoid factor (RF) was significantly reduced after consumption of curcumin in all three relevant studies. None of the studies reported serious adverse effects with curcumin consumption. The present systematic review suggests that curcumin could be used as a safe agent to treat RA. Thus, further validation is justified.
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http://dx.doi.org/10.1007/978-3-030-56153-6_15DOI Listing
August 2021

Antibacterial Activity of Curcumin Against Periodontal Pathogens: A Systematic Review.

Adv Exp Med Biol 2021 ;1291:239-249

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Periodontitis is a chronic inflammatory disease characterized by destruction of the supporting structures of teeth caused by development of dental plaques and accumulation of microorganism around the gingival tissue. Curcumin has been shown to improve clinical parameters in periodontal diseases. However, the efficacy of curcumin in the elimination of periodontal pathogens is not clearly defined. The purpose of this study was to carry out a systematic review of the antibacterial activity of curcumin against periodontal pathogens. An electronic literature search in Medline, Scopus, Science Direct, Web of Science, Cochrane library, and Google scholar was performed up to February 29, 2020, to identify studies assessing the antibacterial activity of curcumin against periodontal pathogens. From 1238 publications, three clinical trials and five in vitro studies met the eligibility criteria. All three clinical studies reported improvement in restoring gingival health in clinical and microbiological parameters, following adjunctive use of curcumin for treatment of periodontitis. All five in vitro studies showed that curcumin could inhibit the growth of bacterial strains. Three of the five in vitro studies evaluated the effect of curcumin on mixed biofilm of periopathogens, which showed a significant inhibitory effect of curcumin on periodontal biofilms. This systematic review found that curcumin has antibacterial activity against periopathogens. The anti-biofilm activity of curcumin is reported as one of the mechanisms for this phenomenon. Curcumin could improve the clinical parameters of periodontal tissue not only by inhibition of the pathogens but also by modulating the host response.
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http://dx.doi.org/10.1007/978-3-030-56153-6_14DOI Listing
August 2021

The Clinical Use of Curcumin for the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Clinical Trials.

Adv Exp Med Biol 2021 ;1291:229-238

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Recurrent aphthous stomatitis (RAS) lesions are inflammatory painful oral ulcers with uncertain etiology. Curcumin acts as an effective anti-inflammatory and antibacterial agent in the treatment of various oral diseases. This systematic review aimed to assess the effects of curcumin on RAS. A systematic search of the medical databases, PubMed, Scopus, ISI, Science Direct, and Google Scholar was performed up to March 30, 2020, to identify clinical trials assessing the effect of curcumin on aphthous ulcers. Nine studies comprising of 469 participants met all criteria and were analyzed. Treatment with curcumin significantly reduced aphthous ulcer size (seven studies), pain intensity (eight studies), number of aphthous ulcers (three studies), erythematous halo (one study), and erythema and exudate of the aphthous (one study). In four studies, the effect of curcumin on aphthous ulcer was assessed in comparison to the effects of the standard medication, triamcinolone. In all of these studies, curcumin had similar beneficial effects on the aphthous ulcer as measured by ulcer size, number, and pain. Only three studies were categorized as high quality using the Jadad scale. Within the limitations of this review, it can be concluded that curcumin may have a beneficial role in the treatment of recurrent aphthous ulcers. However, more randomized clinical trials are needed to validate these findings.
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http://dx.doi.org/10.1007/978-3-030-56153-6_13DOI Listing
August 2021

Does Curcumin Have an Anticaries Effect? A Systematic Review of In Vitro Studies.

Adv Exp Med Biol 2021 ;1291:213-227

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Dental caries is one of the most important oral health problems and a common infectious microbial disease. Streptococcus mutans (S. mutans) has been regarded as the primary etiologic factor in the formation of dental caries. Curcumin (CUR) has an antibacterial action and could be used in the eradication of S. mutans to control dental caries. This systematic review was undertaken with the aim of evaluating the anticaries effect of CUR.

Methods: A comprehensive search was conducted in the PubMed/Medline, Cochrane - CENTRAL, and Scopus databases. Based on the PICO model, studies which evaluated the anticaries effects of CUR up until 24 February 2020 with language restrictions were selected for this systematic review.

Results: From 753 papers found, 13 met the eligibility criteria and were included. In 12 out of 13 included studies, CUR had significant antibacterial and anticaries effects. CUR had inhibitory effects on S. mutans growth, acid production, ATPase and sortase A activity, biomass, viability and metabolism reduction of biofilm, reduced exopolysaccharide production of biofilms, changes in biofilm structure, and had anti-adhesion effects against S. mutans.

Conclusion: This systematic review suggests promising antibacterial and anticaries effects of CUR including inhibition of S. mutans growth, acid production, ATPase and sortase A activity. This review provides unique information regarding the potential role of CUR in the prevention and treatment of dental carries as a natural, accessible, safe, and inexpensive agent to increase oral and dental health. However, clinical randomized controlled trials are needed to confirm these results.
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http://dx.doi.org/10.1007/978-3-030-56153-6_12DOI Listing
August 2021

The Effects of Curcumin in the Treatment of Gingivitis: A Systematic Review of Clinical Trials.

Adv Exp Med Biol 2021 ;1291:179-211

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Different modalities of treatments are available for management of gingival disease but most have adverse effects. Curcumin has anti-inflammatory properties and can be used for management of various inflammatory processes. This systematic review evaluates the effects of curcumin as an adjuvant to oral hygiene on plaque index (PI), gingival index (GI), gingival bleeding index (GBI), and inflammation in patients with gingivitis. A comprehensive search was conducted using PubMed/MEDLINE, Cochrane, SCOPUS, and Google Scholar. Based on the Population, Intervention, Control, and Outcome (PICO) model, clinical trials which tested the effects of curcumin as an adjunctive product or alone in control of gingival inflammation up until 21 February 2020 with language restrictions were selected. From the 422 papers found, 14 met the eligibility criteria. In most of these studies, curcumin treatment achieved significant reductions in PI, GI, GBI, and microbial colony count and was as effective as chlorhexidine mouthwash, with no serious adverse effects. We conclude that treatment with curcumin for gingivitis is safe as a natural herbal compound and is as effective as chlorhexidine mouthwash.
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http://dx.doi.org/10.1007/978-3-030-56153-6_11DOI Listing
August 2021

The Effect of Curcumin in Improving Lipid Profile in Patients with Cardiovascular Risk Factors: A Systematic Review of Clinical Trials.

Adv Exp Med Biol 2021 ;1291:165-177

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Cardiovascular disease (CVD) is a major cause of death worldwide. Lipid abnormalities are one of the major risk factors for CVD. Curcumin is a natural polyphenol with lipid-lowering properties. Therefore, we carried out a systematic review to summarize the randomized controlled trials (RCTs) investigating the effect of curcumin on lipid profile in patients at risk of CVD. A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar up to March 1, 2020, to identify controlled clinical trials assessing the effects of curcumin on lipid profile in patients at risk of CVD. From 1051 initially identified studies, 22 met the eligibility criteria. Curcumin supplementation significantly reduced at least one of the lipid profile indices (triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol) in 15 studies and improved more than one index in five studies. However, curcumin had no effect on any of lipid profile indices in seven studies. Overall, studies using a bioavailable formulation of curcumin had a better impact on the lipid profile. The findings of this systematic review showed that curcumin supplementation significantly reduced at least one of the lipid profile indices in more than two-thirds of the included studies. Curcumin might be used as an accessible, inexpensive, and safe agent to reduce risk of CVD. More randomized, clinical controlled trials are needed to verify these results.
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http://dx.doi.org/10.1007/978-3-030-56153-6_10DOI Listing
August 2021

Effect of Curcumin on Glycemic Control in Patients with Type 2 Diabetes: A Systematic Review of Randomized Clinical Trials.

Adv Exp Med Biol 2021 ;1291:139-149

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition, which carries considerable morbidity and mortality. There is growing evidence that curcumin could modulate glucose homeostasis and improve vascular risk in patients with T2DM. The aim of this systematic review was to study the effect of curcumin on glycemic indices in patients with diabetes. A comprehensive search was conducted in PubMed, Scopus, Embase, and Google Scholar up to March 5, 2020, to identify randomized control trials investigating the effect of curcumin supplementation on glycemic indices including fasting blood glucose (FBS), hemoglobin A1c (HbA1C), and the homeostatic model assessment for insulin resistance (HOMA-IR). Eleven articles comprising 1131 individuals with T2DM were included in the study. Treatment with curcumin significantly reduced the level of FBS and HbA1c in 8 and 7 studies, respectively. HOMA-IR was evaluated in five studies, and this was reduced significantly by curcumin supplementation in three of those studies. Patients who took curcumin supplementation over longer periods (≥12 weeks) showed a significant reduction in glycemic indices. The current systematic review showed that curcumin can improve glycemic control in patients with T2DM. However, further studies are required to determine the optimum conditions for these effects of curcumin, particularly regarding readouts of insulin resistance.
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http://dx.doi.org/10.1007/978-3-030-56153-6_8DOI Listing
August 2021

The Effect of Curcumin Supplemsentation on Anthropometric Indices in Overweight and Obese Individuals: A Systematic Review of Randomized Controlled Trials.

Adv Exp Med Biol 2021 ;1291:121-137

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Curcumin is an active molecule present in turmeric and is the main therapeutic compound. There is growing evidence that curcumin could affect various anthropometric indices. We performed a systematic review to evaluate the efficacy of curcumin supplementation on anthropometric indices in obese and overweight individuals.

Methods: A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Google Scholar from inception up to February 2020 to identify randomized controlled trials investigating the effect of curcumin supplementation on anthropometric indices including body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), arm circumference (AC), waist-hip ratio (WHR), total body fat (TBF), and visceral fat (VF) in obese and overweight individuals. The Jadad scale was used to assess the quality of the included studies.

Result: Twenty-eight randomized controlled trials, comprising 2168 participants, were included in the systematic review. The results of 16 papers indicated that curcumin reduced at least one of the anthropometric indices among individuals with a BMI ≥ 25 kg/m. Nevertheless, 12 articles showed that curcumin supplementation was not effective in any of the measured anthropometric factors. The included trials exhibited substantial heterogeneity in terms of the treatment protocol, follow-up duration, curcumin dosage, and background diseases of the participants.

Conclusion: Clinical trials that have independently examined the effects of curcumin in obese or overweight individuals are limited. However, available studies indicate that curcumin has beneficial impacts on various anthropometric indices. Further trials with longer duration of interventions are needed to confirm these findings.
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http://dx.doi.org/10.1007/978-3-030-56153-6_7DOI Listing
August 2021

The Effects of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptydilpeptidase-4 Inhibitors on Blood Pressure and Cardiovascular Complications in Diabetes.

J Diabetes Res 2021 30;2021:6518221. Epub 2021 Jun 30.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are a class of newly introduced antidiabetic medications that potentially lower blood glucose by several molecular pathways. DPP-4 inhibitors are the other type of novel antidiabetic medications which act by preventing GLP-1 inactivation and thereby increasing the activity levels of GLP-1, leading to more glucose-induced insulin release from islet -cells and suppression of glucagon release. Most patients with diabetes have concurrent hypertension and cardiovascular disorder. If antihyperglycemic agents can attenuate the risk of hypertension and cardiovascular disease, they will amplify their overall beneficial effects. There is conflicting evidence on the cardiovascular benefits of GLP-1R induction in laboratory studies and clinical trials. In this study, we have reviewed the main molecular mechanisms by which GLP-1R induction may modulate the cardiovascular function and the results of cardiovascular outcome clinical trials.
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http://dx.doi.org/10.1155/2021/6518221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263148PMC
June 2021

Soluble Neuropilin-1 Response to Hypoglycemia in Type 2 Diabetes: Increased Risk or Protection in SARS-CoV-2 Infection?

Front Endocrinol (Lausanne) 2021 23;12:665134. Epub 2021 Jun 23.

Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.

Introduction: Neuropilin-1(NRP1) is a cofactor that enhances SARS-CoV-2 coronavirus cell infectivity when co-expressed with angiotensin-converting enzyme 2(ACE2). The Renin-Angiotensin System (RAS) is activated in type 2 diabetes (T2D); therefore, the aim of this study was to determine if hypoglycaemia-induced stress in T2D would potentiate serum NRP1(sNRP1) levels, reflecting an increased risk for SARS-CoV-2 infection.

Methods: A case-control study of aged-matched T2D (n = 23) and control (n = 23) subjects who underwent a hyperinsulinemic clamp over 1-hour to hypoglycemia(<40mg/dl) with subsequent timecourse of 4-hours and 24-hours. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement determined RAS-related proteins: renin (REN), angiotensinogen (AGT), ACE2, soluble NRP1(sNRP1), NRP1 ligands (Vascular endothelial growth factor, VEGF and Class 3 Semaphorins, SEM3A) and NRP1 proteolytic enzyme (A Disintegrin and Metalloproteinase 9, ADAM9).

Results: Baseline RAS overactivity was present with REN elevated and AGT decreased in T2D (p<0.05); ACE2 was unchanged. Baseline sNRP1, VEGF and ADAM9 did not differ between T2D and controls and remained unchanged in response to hypoglycaemia. However, 4-hours post-hypoglycemia, sNRP1, VEGF and ADAM9 were elevated in T2D(p<0.05). SEMA3A was not different at baseline; at hypoglycemia, SEMA3A decreased in controls only. Post-hypoglycemia, SEMA3A levels were higher in T2D versus controls. sNRP1 did not correlate with ACE2, REN or AGT. T2D subjects stratified according to ACE inhibitor (ACEi) therapies showed no difference in sNRP1 levels at either glucose normalization or hypoglycaemia.

Conclusion: Hypoglycemia potentiated both plasma sNRP1 level elevation and its ligands VEGF and SEMA3A, likely through an ADAM9-mediated mechanism that was not associated with RAS overactivity or ACEi therapy; however, whether this is protective or promotes increased risk for SARS-CoV-2 infection in T2D is unclear.

Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03102801.
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http://dx.doi.org/10.3389/fendo.2021.665134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261232PMC
July 2021

Type 2 Diabetes Coagulopathy Proteins May Conflict With Biomarkers Reflective of COVID-19 Severity.

Front Endocrinol (Lausanne) 2021 25;12:658304. Epub 2021 Jun 25.

Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.

Objective: Detailed proteomic analysis in a cohort of patients with differing severity of COVID-19 disease identified biomarkers within the complement and coagulation cascades as biomarkers for disease severity has been reported; however, it is unclear if these proteins differ sufficiently from other conditions to be considered as biomarkers.

Methods: A prospective, parallel study in T2D (n = 23) and controls (n = 23). A hyperinsulinemic clamp was performed and normoglycemia induced in T2D [4.5 ± 0.07 mmol/L (81 ± 1.2 mg/dl)] for 1-h, following which blood glucose was decreased to ≤2.0 mmol/L (36 mg/dl). Proteomic analysis for the complement and coagulation cascades were measured using Slow Off-rate Modified Aptamer (SOMA)-scan.

Results: Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2D controls for platelet degranulation [Neutrophil-activating peptide-2 (p = 0.014), Thrombospondin-1 (p = 0.012), Platelet factor-4 (p = 0.007), and Kininogen-1 (p = 0.05)], whilst 3 of 16 proteins differed for complement and coagulation cascades [Coagulation factor IX (p < 0.05), Kininogen-1 (p = 0.05), and Heparin cofactor-2 (p = 0.007)]; STRING analysis demonstrated the close relationship of these proteins to one another. Induced euglycemia in T2D showed no protein changes baseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p < 0.014), platelet factor-4 (p < 0.01), Platelet basic protein (p < 0.008), and Vitamin K-dependent protein-C (p < 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p < 0.0002)].

Conclusion: Seven of 34 proteins suggested to be biomarkers of COVID-19 severity within the platelet degranulation and complement and coagulation cascades differed in T2D controls, with further changes occurring at hypoglycemia, suggesting that validation of these biomarkers is critical. It is unclear if these protein changes in T2D may predict worse COVID-19 disease for these patients.

Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT03102801.
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http://dx.doi.org/10.3389/fendo.2021.658304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267927PMC
July 2021

Love is in the hair: arginine methylation of human hair proteins as novel cardiovascular biomarkers.

Amino Acids 2021 Jun 28. Epub 2021 Jun 28.

Department of Biomedical Sciences, University of Hull, Cottingham Rd, Hull, HU6 7RX, UK.

Cardiovascular disease is the major cause of death worldwide. Extensive cardiovascular biomarkers are available using blood tests but very few, if any, investigations have described non-invasive tests for cardiovascular biomarkers based on readily available hair samples. Here we show, first, that human hair proteins are post-translationally modified by arginine methylation (ArgMe). Using western blot, proteomic data mining and mass spectrometry, we identify several ArgMe events in hair proteins and we show that keratin-83 is extensively modified by ArgMe in the human hair. Second, using a preliminary cohort (n = 18) of heterogenous healthy donors, we show that the levels of protein ArgMe in hair correlate with serum concentrations of a well-established cardiovascular biomarker, asymmetric dimethylarginine (ADMA). Compared to blood collection, hair sampling is cheaper, simpler, requires minimal training and carries less health and safety and ethical risks. For these reasons, developing the potential of hair protein ArgMe as clinically useful cardiovascular biomarkers through further research could be useful in future prevention and diagnosis of cardiovascular disease.
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http://dx.doi.org/10.1007/s00726-021-03024-5DOI Listing
June 2021

Predictors of diabetes-related distress before and after FreeStyle Libre-1 use: Lessons from the Association of British Clinical Diabetologists nationwide study.

Diabetes Obes Metab 2021 Oct 29;23(10):2261-2268. Epub 2021 Jun 29.

City Hospital, Birmingham, UK.

Aim: To identify the baseline demographic and clinical characteristics associated with diabetes-related distress (DRD) and factors associated with improvement in DRD after initiating use of the FreeStyle Libre (FSL) in people living with type 1 diabetes (T1D).

Methods: The study was performed using baseline and follow-up data from the Association of British Clinical Diabetologists nationwide audit of people with diabetes who initiated use of the FSL in the United Kingdom. DRD was assessed using the two-item diabetes-related distress scale (DDS; defined as the average of the two-item score ≥3). People living with T1D were categorized into two groups: those with high DRD, defined as an average DDS score ≥3 and those with lower DRD, defined as a DDS score <3. We used a gradient-boosting machine-learning (GBM) model to identify the relative influence (RI) of baseline variables on average DDS score.

Results: The study population consisted of 9159 patients, 96.6% of whom had T1D. The median (interquartile range [IQR]) age was 45.1 (32-56) years, 50.1% were women, the median (IQR) baseline body mass index was 26.1 (23.2-29.6) kg/m and the median (IQR) duration of diabetes was 20 (11-32) years. The two components of the DDS were significantly correlated (r  = 0.73; P < 0.0001). Higher DRD was prevalent in 53% (4879/9159) of people living with T1D at baseline. In the GBM model, the top baseline variables associated with average DDS score were baseline glycated haemoglobin (HbA1c; RI = 51.1), baseline Gold score (RI = 23.3), gender (RI = 7.05) and fear of hypoglycaemia (RI = 4.96). Follow-up data were available for 3312 participants. The top factors associated with improvement in DDS score following use of the FSL were change in Gold score (RI = 28.2) and change in baseline HbA1c (RI = 19.3).

Conclusions: In this large UK cohort of people living with T1D, diabetes distress was prevalent and associated with higher HbA1c, impaired awareness of hypoglycaemia and female gender. Improvement in glycaemic control and hypoglycaemia unawareness with the use of the FSL was associated with improvement in DRD in people living with T1D.
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http://dx.doi.org/10.1111/dom.14467DOI Listing
October 2021

Roux-en-Y gastric bypass-induced bacterial perturbation contributes to altered host-bacterial co-metabolic phenotype.

Microbiome 2021 06 14;9(1):139. Epub 2021 Jun 14.

Division of Digestive Disease, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, SW7 2AZ, UK.

Background: Bariatric surgery, used to achieve effective weight loss in individuals with severe obesity, modifies the gut microbiota and systemic metabolism in both humans and animal models. The aim of the current study was to understand better the metabolic functions of the altered gut microbiome by conducting deep phenotyping of bariatric surgery patients and bacterial culturing to investigate causality of the metabolic observations.

Methods: Three bariatric cohorts (n = 84, n = 14 and n = 9) with patients who had undergone Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or laparoscopic gastric banding (LGB), respectively, were enrolled. Metabolic and 16S rRNA bacterial profiles were compared between pre- and post-surgery. Faeces from RYGB patients and bacterial isolates were cultured to experimentally associate the observed metabolic changes in biofluids with the altered gut microbiome.

Results: Compared to SG and LGB, RYGB induced the greatest weight loss and most profound metabolic and bacterial changes. RYGB patients showed increased aromatic amino acids-based host-bacterial co-metabolism, resulting in increased urinary excretion of 4-hydroxyphenylacetate, phenylacetylglutamine, 4-cresyl sulphate and indoxyl sulphate, and increased faecal excretion of tyramine and phenylacetate. Bacterial degradation of choline was increased as evidenced by altered urinary trimethylamine-N-oxide and dimethylamine excretion and faecal concentrations of dimethylamine. RYGB patients' bacteria had a greater capacity to produce tyramine from tyrosine, phenylalanine to phenylacetate and tryptophan to indole and tryptamine, compared to the microbiota from non-surgery, normal weight individuals. 3-Hydroxydicarboxylic acid metabolism and urinary excretion of primary bile acids, serum BCAAs and dimethyl sulfone were also perturbed following bariatric surgery.

Conclusion: Altered bacterial composition and metabolism contribute to metabolic observations in biofluids of patients following RYGB surgery. The impact of these changes on the functional clinical outcomes requires further investigation. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01086-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201742PMC
June 2021

The Effect of Combined Vitamin C and Vitamin E Supplementation on Oxidative Stress Markers in Women with Endometriosis: A Randomized, Triple-Blind Placebo-Controlled Clinical Trial.

Pain Res Manag 2021 26;2021:5529741. Epub 2021 May 26.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Endometriosis is a chronic and estrogen-dependent pelvic inflammatory disease, which may have various causes, such as oxidative stress. Dysmenorrhea, dyspareunia, and pelvic pain are well-known symptoms of endometriosis. The present clinical trial assessed the role of supplementation with antioxidant vitamins on the indices of oxidative stress as well as the severity of pain in women with endometriosis.

Materials And Methods: We enrolled 60 reproductive-aged (15-45 years) women with pelvic pain in this triple-blind clinical trial. They had 1-3 stages of laparoscopic-proven endometriosis. The participants were randomized to group A ( = 30), given vitamin C (1000 mg/day, 2 tablets of 500 mg each) and vitamin E (800 IU/day, 2 tablets of 400 IU each) combination, or group B ( = 30), given placebo pills daily for 8 weeks.

Results: Following treatment with vitamin C and vitamin E, we found a significant reduction in MDA and ROS compared with the placebo group. There was no significant decline in total antioxidant capacity after treatment. However, the severity of pelvic pain ( value <0.001), dysmenorrhea ( value <0.001), and dyspareunia ( value <0.001) significantly decreased in the treatment group after 8 weeks of supplementation.

Conclusions: The present findings support the potential role of antioxidants in the management of endometriosis. The intake of vitamin C and vitamin E supplements effectively reduced dysmenorrhea severity and improved dyspareunia and severity of pelvic pain.
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http://dx.doi.org/10.1155/2021/5529741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172324PMC
July 2021

The Effect of Free Androgen Index on the Quality of Life of Women With Polycystic Ovary Syndrome: A Cross-Sectional Study.

Front Physiol 2021 24;12:652559. Epub 2021 May 24.

Department of Academic Diabetes, Endocrinology, and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom.

Free androgen index (FAI) and anti-Mullerian hormone (AMH) are independently associated with polycystic ovary syndrome (PCOS). This study aimed to describe the relationship between these two markers and health-related quality of life (HR-QoL) in women with PCOS. This cross-sectional study consisted of 81 women in the Hull PCOS biobank, who fulfilled the Rotterdam consensus criteria for the diagnosis of PCOS. The primary outcome was to measure the various domains of the QoL in the modified polycystic ovary syndrome questionnaire (MPCOSQ). Mean age of the study participants was 28 ± 6.0 years, mean body mass index (BMI) 33.5 ± 7.8 kg/m, mean FAI (6 ± 5.5), free testosterone (2.99 ± 0.75) and mean AMH (3.5 ± 0.8 units). In linear regression analysis, the FAI was associated with overall mean MPCOSQ score (Beta = 0.53, -value = 0.0002), and with depression (Beta = 0.45, -value = 0.01), hirsutism (Beta = 0.99, -value = 0.0002) and menstrual irregularity (Beta = 0.31, -value = 0.04). However, with adjustment for age and BMI, FAI was only associated with the hirsutism domain (Beta = 0.94, -value = 0.001) of the MPCOSQ. FAI was also associated with the weight domain (Beta = 0.63 -value = 0.005) of MPCOSQ. However, AMH was not associated with the overall mean MPCOSQ score or with any of its domains. FAI but not AMH was associated with QoL in women with PCOS, and this effect was mediated by BMI.
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http://dx.doi.org/10.3389/fphys.2021.652559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181761PMC
May 2021

Antioxidative Potentials of Incretin-Based Medications: A Review of Molecular Mechanisms.

Oxid Med Cell Longev 2021 27;2021:9959320. Epub 2021 Apr 27.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Glucagon-like peptide 1 receptor agonists and dipeptidyl-peptidase 4 inhibitors are medications used for managing diabetes, mimicking the metabolic effects of incretin hormones. Recent evidence suggests that these medications have antioxidative potentials in the diabetic milieu. The pathophysiology of most diabetic complications involves oxidative stress. Therefore, if incretin-based antidiabetic medications can alleviate the free radicals involved in oxidative stress, they can potentially provide further therapeutic effects against diabetic complications. However, the molecular mechanisms by which these medications protect against oxidative stress are not fully understood. In the current review, we discuss the potential molecular mechanisms behind these pharmacologic agents' antioxidative properties.
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http://dx.doi.org/10.1155/2021/9959320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099522PMC
April 2021
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