Protective Effects of Curcumin in the Reproductive System: Anti-toxic, Semen Cryopreservative, and Contraceptive Actions.

Human daily exposure to various chemical and biological agents is growing due to modern life, and most of these chronic or acute exposures lead to important recognized toxicities. Multiple tissues and body systems could be affected following these exposures and among them is the human reproductive system, which is very vulnerable to toxins. Here we focus mainly on the male reproductive system, and available data show that various exogenous materials could have negative effects on male reproductive parameters. Interestingly, the well-known antioxidant natural product curcumin may have properties which could diminish these toxic effects. Curcumin has also shown some promise in the cryoprotection of sperm samples through its antioxidant potential. Finally, limited data exists on the putative contraceptive activity of curcumin. This narrative review aims to appraise the activity of curcumin within these topics through the available data.

Carbon-based Nanomaterials and Curcumin: A Review of Biosensing Applications.

Curcumin, the main active constituent of turmeric (Curcuma longa L.), is a naturally occurring phenolic compound with a wide variety of pharmacological activities. Although it has multiple pharmaceutical properties, its bioavailability and industrial usage are hindered due to rapid hydrolysis and low water solubility. Due to the growing market of curcumin, exact determination of curcumin in trade and human biological samples is important for monitoring therapeutic actions. Different nanomaterials have been suggested for sensing curcumin; and in this case, carbon-based nanomaterials (CNMs) are one of the most outstanding developments in nanomedicine, biosensing, and regenerative medicine. There are a considerable number of reports which have shown interesting potential of CNMs-based biosensors in the sensitive and selective detection of curcumin. Therefore, this review aims to increase understanding the interaction of curcumin with CNMs in the context of biosensing.

Gender Susceptibility to COVID-19 Mortality: Androgens as the Usual Suspects?

Identification of the causal risk factors of COVID-19 would allow better risk stratification and designing effective therapies. Epidemiological data have shown a higher incidence and mortality of COVID-19 in males compared to females. Here, we have used logistic regression analysis modeling to determine the association between gender and COVID-19 mortality in the Iranian population. The records of 2293 patients with COVID-19 infection were analyzed. The odds of death due to COVID-19 were 1.7 times higher in males compared to females after adjustment for age and background diseases. The gender difference was mainly observed at higher ages, suggesting an adjusted 2.32-fold higher risk of mortality in males aged >59.5 years old compared to females within the same age group. This finding suggests the male gender is a potential predisposing factor for mortality due to COVID-19 infection. The potential role of male hormones, particularly testosterone, as therapeutic targets deserves further investigation.

Antidiabetic Properties of Curcumin: Insights on New Mechanisms.

Plant extracts have been used to treat a wide range of human diseases. Curcumin, a bioactive polyphenol derived from Curcuma longa L., exhibits therapeutic effects against diabetes while only negligible adverse effects have been observed. Antioxidant and anti-inflammatory properties of curcumin are the main and well-recognized pharmacological effects that might explain its antidiabetic effects. Additionally, curcumin may regulate novel signaling molecules and enzymes involved in the pathophysiology of diabetes, including glucagon-like peptide-1, dipeptidyl peptidase-4, glucose transporters, alpha-glycosidase, alpha-amylase, and peroxisome proliferator-activated receptor gamma (PPARγ). Recent findings from in vitro and in vivo studies on novel signaling pathways involved in the potential beneficial effects of curcumin for the treatment of diabetes are discussed in this review.

A Review of Monoclonal Antibody-Based Treatments in Non-small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer worldwide. It metastasizes rapidly and has a poor prognosis. The first-line treatment for most patients is a combination of chemotherapy and radiation. In many subjects, using targeted treatments alongside chemoradiation has shown a better outcome in terms of progression and quality of life for patients. These targeted treatments include small biological inhibiting molecules and monoclonal antibodies. In this review, we have assessed studies focused upon the treatment of non-small cell lung cancer. Some therapies are approved, such as bevacizumab and atezolizumab, while some are still in clinical trials, such as ficlatuzumab and ipilimumab, and others have been rejected due to inadequate disease control, such as figitumumab.

Effects of Curcuminoids on Systemic Inflammation and Quality of Life in Patients with Colorectal Cancer Undergoing Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Colorectal cancer (CRC) is the third and the fourth most common cancer in Iranian men and women, respectively. Curcuminoids are known to exertprotective effects against several kinds of cancers. We aim to assess the effects of curcuminoids on serum pro- and anti-inflammatory cytokines and quality of life in patients with colorectal cancer undergoing chemotherapy. MATERIAL AND METHODS: This study was a double-blind placebo-controlled trial in patients with CRC (stage 3) aged ≥20 years, who had chemotherapy after the surgery and were referred to Baqiyatallah Oncology Clinic. Patients were randomly assigned to the treatment group receiving curcuminoids capsules (500 mg/day) (n = 36), or the control group taking placebo capsules (n = 36) for 8 weeks. Erythrocyte sedimentation rate (ESR) and serum levels of C-reactive protein (CRP) and 12 pro- and anti-inflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1α (IL-1α), IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP-1), interferon γ (IFN-γ), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF)] were measured at baseline and at the end of the intervention. The EORTC-QLQ-C30 instrument was used to assess the quality of life before and after the intervention. Statistical analyses were performed using SPSS software. RESULTS: A total of 67 subjects completed the study as three and two subjects were lost to follow-up in the curcuminoid and placebo groups, respectively. A significant change in CRP (p = 0.002) and ESR (p = 0.0001) was observed in patients supplemented with curcuminoids at the end of 8 weeks compared to placebo. Moreover, IL-1α showed a decreasing trend after curcuminoid supplementation compared to placebo (p = 0.077). A significant improvement in functional (p = 0.002) and global quality of life (p = 0.020) scales was observed in the curcuminoid group. CONCLUSIONS: The results showed that curcuminoids supplementation for a period of 8 weeks (500 mg/day) can improve ESR and serum levels of CRP in stage-3 CRC subjects and improve the global quality of life and functional scales compared to placebo.

Cytotoxicity evaluation of curcumin-loaded affibody-decorated liposomes against breast cancerous cell lines.

Curcumin is known as an effective anticancer herbal medicine but unfortunately, its bioavailability is poor which necessitate efforts for developing more efficient and specific delivery systems. Human epidermal growth factor receptor 2 (HER 2) due to its overexpression in various types of cancers, is demonstrated to be a good candidate as a target for anticancer therapy. In this study, cytotoxicity of curcumin encapsulated in ZHER2:342 Affibody-decorated liposome was investigated against SKBR3 and MCF-7 cancerous cell lines. Curcumin-containing liposomes were prepared from soybeans lecetin and cholesterol by thin-film hydration method. Affibody ZHER2:342 molecules via C-terminal cysteine residue were conjugated covalently to the prepared liposomes. Particle size analysis was performed using atomic force microscopy (AFM) and dynamic light scattering (DLS). Curcumin loading was measured using UV-Vis spectrophotometry and cytotoxic activity of curcumin formulations against cancerous cell lines was investigated by MTT assay. Induction of apoptosis was investigated using flow cytometry through Annexin V staining. Particle analysis showed the formation of spherical liposomes with a mean diameter of about 150 nm. Cytotoxic activity of curcumin was improved by its encapsulation in both liposomes and affibody-decorated liposomes. The Annexin V staining indicated the induction of apoptosis by affibody-decorated liposomes in both MCF-7 and SKBR3 cells. Decoration of curcumin-loaded liposomes with affibody ZHER2:342 may improve curcumin apoptotic function independently of HER2 expression level.

Protective effect of Zataria multiflora Boiss. and its main compound, rosmarinic acid, against malathion induced oxidative stress and apoptosis in HepG2 cells.

Malathion (MT) is one of the most widely used organophosphorus insecticides which induces toxicity through oxidative stress induction, free radical production and acetylcholinesterase inhibition. In this work, HepG2 cells were used to determine the effect of Zataria multiflora methanolic extract (MEZM) and rosmarinic acid (RA) on MT-induced cytotoxicity, oxidative stress, and apoptosis. Total phenolic content (TPC) and total flavonoid content (TFC) were determined and plant was further standardized based on RA content using HPLC method. The cultured HepG2 cells were pretreated with MEZM (1 µg/ml) and RA (0.1 µg/ml) for 4 h and exposed to MT (100 µM). Cell viability, oxidative stress biomarkers, ROS production, and cell death were examined after 24 h. The amount of RA was determined 73.48 mg/g dried extract. IC50 values of MEZM and MT were 368.56 µg/ml and 99.43 µM, respectively. Pretreatment with MEZM and RA decreased the cytotoxicity, oxidative stress, and cell percentage in the late apoptosis and necrosis stages induced by MT. There was no significant difference between MEZM and RA effects. The present study showed the significant protective effects of MEZM against toxicity induced by MT in hepatocytes which can be attributed to the plant antioxidant constituents including RA.

Carbon nanomaterials and amyloid-beta interactions: potentials for the detection and treatment of Alzheimer's disease?

Carbon-based nanomaterials have unique physicochemical properties relevant to the diagnosis and treatment of various diseases. There have been many reports indicating that carbon nanomaterials (CNMs) can interact and perturb biomolecules such as proteins and amyloid structures. This review is an attempt to reflect the role of CNMs in the treatment and detection of Alzheimer's disease (AD). The potential of CNMs in the field of neuroscience has also been reviewed. The exposure to CNMs ends up with effective radical and peptide scavenging structures, which, in turn, inhibit further formation and progression of amyloid fibrils. However, the effect of CNMs on initial nucleation and lag phase in this process may promote fibrillation. We have discussed the controversy that whether CNMs promote or inhibit the formation of amyloid beta (Aß) fibrils to help preventing their toxicity or enhancing their therapeutic effects.

Biomedical applications of carbon nanomaterials: Drug and gene delivery potentials.

One of the major components in the development of nanomedicines is the choice of the right biomaterial, which notably determines the subsequent biological responses. The popularity of carbon nanomaterials (CNMs) has been on the rise due to their numerous applications in the fields of drug delivery, bioimaging, tissue engineering, and biosensing. Owing to their considerably high surface area, multifunctional surface chemistry, and excellent optical activity, novel functionalized CNMs possess efficient drug-loading capacity, biocompatibility, and lack of immunogenicity. Over the past few decades, several advances have been made on the functionalization of CNMs to minimize their health concerns and enhance their biosafety. Recent evidence has also implied that CNMs can be functionalized with bioactive peptides, proteins, nucleic acids, and drugs to achieve composites with remarkably low toxicity and high pharmaceutical efficiency. This review focuses on the three main classes of CNMs, including fullerenes, graphenes, and carbon nanotubes, and their recent biomedical applications.

Protective effects of curcumin against aflatoxicosis: A comprehensive review.

Aflatoxicosis is a deleterious medical condition that results from aflatoxins (AFs) or ochratoxins (OTs). Contamination with these toxins exerts detrimental effects on the liver, kidneys, reproductive organs, and also on immunological and cardiovascular systems. Aflatoxicosis is closely associated with overproduction of reactive oxygen species (ROS) as key contributors to oxidative and nitrosative stress responses, and subsequent damages to lipids, proteins, RNA, and DNA. The main target organ for AF toxicity is the liver, where DNA adducts, degranulation of endoplasmic reticulum, increased hepatic lipid peroxide, GSH depletion, mitochondrial dysfunction, and reduction of enzymatic and non-enzymatic antioxidants are manifestations of aflatoxicosis. Curcuma longa L. (turmeric) is a medicinal plant widely utilized all over the world for culinary and phytomedical purposes. Considering the antioxidant characteristic of curcumin, the main active component of turmeric, this review is intended to critically summarize the available evidence supporting possible effectiveness of curcumin against aflatoxicosis. Curcumin can serve as a promising candidate for attenuation of the adverse consequences of aflatoxicosis, acting mainly through intrinsic antioxidant effects aroused from its structure, modulation of the immune system as reflected by interleukin-1ß and transforming growth factor-ß, and interfering with AF's biotransformation by cytochrome P450 isoenzymes CYP1A, CYP3A, CYP2A, CYP2B, and CYP2C.

Reproductive Toxicity of Nanoparticles: A Comprehensive Review.

The unique characteristics of nanoparticles (NPs) have captivated scientists in various fields of research. However, their safety profile has not been fully scrutinized. In this regard, the effects of NPs on the reproductive system of animals and humankind have been a matter of concern. In this article, we will review the potential reproductive toxicity of various types of NPs, including carbon nanomaterials, dendrimers, quantum dots, silica, gold, and magnetic nanoparticles, reported in the literature. We also mention some notable cases where NPs have elicited beneficial effects on the reproductive system. This review provides extensive insight into the effects of various NPs on sperm and ovum and the outcomes of their passage through blood-testis and placental barriers and accumulation in the reproductive organs.

Preparing and assessing the physiochemical properties of curcumin niosomes and evaluating their cytotoxicity in 3T3 and MCF-7 cell lines.

OBJECTIVE: Application of vesicular drug delivery systems has made major progress in pharmaceutical science and technology. Niosomal drug delivery is potentially efficient to improve the pharmacokinetic and pharmacological properties of many compounds. Curcumin (CUR) has several documented anticancer activities; however, it has a low bioavailability that necessitates the development of efficient delivery systems. Accordingly, different niosomal preparations were prepared and evaluated in the present study to find a suitable delivery system. MATERIALS AND METHODS: Span and Tween 20, 40, 60, and 80 were employed with various concentrations of cholesterol for studying the ability to form curcumin-loaded niosomes. Multiple characterization techniques including visual evaluation, particle size analysis, stability, encapsulation efficiency (EE), and release profile were studied. Cytotoxicity of curcumin niosomes on MCF-7 and 3T3 cell lines was determined using MTT assay. RESULTS: Visual and particle size analysis indicated the formation of seven niosomal formulations in the micron size range, while the formulation consisted of Tween 40/cholesterol (50/50 M%) with 0.05% w/v CUR had an average diameter of 475 nm. The latter formulation was selected and it had EE of 78.5%. The CUR release profile showed 18.7% release over a period of 300 min. The MTT results showed that CUR incorporation significantly increased the cytotoxicity of niosomes and the extent of toxicity was higher in MCF-7 cells. CONCLUSION: In this study, a simple niosomal formulation was developed for CUR loading with favorable physicochemical properties. The presented niosomal curcumin had also considerable effects in cell toxicity studies, which can be suggested for future anticancer studies.

Optimization of immobilization of Pseudomonas cepacia lipase on multiwalled carbon nanotubes functionalized with glycyrrhizin and Tween 80.

In the present study, multiwalled carbon nanotubes (MWCNTs) were functionalized with glycyrrhizin and Tween 80 and applied for immobilization of Pseudomonas cepacia lipase (PcL). Characterization of f-MWCNTs was performed through Fourier-transform infrared spectroscopy, thermal gravimetric, field emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy analysis. The optimum specific activity of immobilized PcL (studied by Plackett-Burman statistical design) occurred at 0.3 mg/mL of f-MWCNTs, 25 mM of phosphate buffer (pH 6.0), 15 min sonication time, 8 U/mL of enzyme concentration, and 24 h immobilization time at 4 °C in the absence of glutaraldehyde. In these conditions, the specific activity was 16.57 ± 0.71 U/mg, which was very close to the predicted amount (16.62 ± 0.64 U/mg). The results of thermal and pH stability showed that the stability of immobilized PcL was higher than that of the free PcL. The activity of immobilized PcL on f-MWCNTs held 93% after being incubated for 60 min at 70 °C. Moreover, the immobilized PcL on f-MWCNTs retained about 65% of its initial activity after 30 days of storage at 25 °C. In addition, about 50% of initial activity of immobilized PcL retained after 10 cycles of uses. Therefore, f-MWCNTs could be introduced as suitable support for enzymes immobilization.

Carbon based nanomaterials for the detection of narrow therapeutic index pharmaceuticals.

Precise detection of important pharmaceuticals with narrow therapeutic index (NTI) is very critical as there is a small window between their effective dose and the doses at which the adverse reactions are very likely to appear. Regarding the fact that various pharmacokinetics will be plausible while considering pharmacogenetic factors and also differences between generic and brand name drugs, accurate detection of NTI will be more important. Current routine analytical techniques suffer from many drawbacks while using novel biosensors can bring up many advantages including fast detection, accuracy, low cost with simple and repeatable measurements. Recently the well-known carbon Nano-allotropes including carbon nanotubes and graphenes have been widely used for development of different Nano-biosensors for a diverse list of analytes because of their great physiochemical features such as high tensile strength, ultra-light weight, unique electronic construction, high thermo-chemical stability, and an appropriate capacity for electron transfer. Because of these exceptional properties, scientists have developed an immense interest in these nanomaterials. In this case, there are important reports to show the effective Nano-carbon based biosensors in the detection of NTI drugs and the present review will critically summarize the available data in this field.

Conjugates of Curcumin with Graphene and Carbon Nanotubes: A Review on Biomedical Applications.

In the last decade, the use of carbon nanotubes and graphenes has been on the rise for various nanobiotechnological applications. Owing to their special characteristics, these two nanostructures of carbon allotropes have been studied for their capacity in the detection and treatment of many diseases. On the other hand, curcumin, a well-known antioxidant and anticancer natural product, is being extensively studied for numerous medicinal applications. Interestingly, many reports have shown great potentials of conjugates of curcumin and carbon nanotubes or graphenes. These conjugates, when properly designed and functionalized with biomolecules, could represent the valuable properties of each component alone while they could be effective in overcoming the poor solubility issues of both curcumin and Carbon Nanomaterials (CNMs). In this case, curcumin conjugates with CNMs seem to be very promising in biosensing applications and the detection of many biomolecules, especially, curcumin has been reported to be very effective with these conjugates. Also, the delivery of curcumin using functionalized SWCNTs was evaluated for its ability to load and release curcumin, to protect curcumin from degradation and to enhance its solubility. It is proposed that other properties of these conjugates are still to be discovered and the interdisciplinary approaches among biology, medicine, chemistry, and material engineering will accelerate the applications of these novel materials. This review aims to summarize the findings on the applications of CNM conjugates of curcumin.

Effects of curcuminoids on inflammatory status in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: Nonalcoholic fatty liver diseases (NAFLD) is a highly prevalent disease that is closely associated with several cardiometabolic complications. The potential anti-inflammatory role of curcuminoids that have already been reported to reduce hepatic steatosis, in patients with NAFLD was explored in this study. METHODS: This double-blind, randomized placebo-controlled trial was conducted for a period of 8 weeks in patients with NAFLD. Subjects (n = 55) were randomly allocated to receive either curcuminoids or placebo. The curcuminoids group received one capsule containing 500 mg curcuminoids (plus 5 mg piperine to increase intestinal absorption) per day for 8 weeks and the control group received matched placebo capsules for the same period. Liver ultrasonography was performed to assess the severity of hepatic steatosis at baseline and the study end. Serum levels of cytokines including interleukin-1α, interleukin-1ß, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon γ, vascular endothelial growth factor and epidermal growth factor were measured before and after the intervention. RESULTS: The two groups were comparable in demographic features at baseline. The results showed that supplementation with curcuminoids could decrease weight compared to the placebo group (p = 0.016) in patients with NAFLD. Curcuminoids supplementation improved the severity of NAFLD according to the ultrasound results (p = 0.002). Moreover, serum concentrations of TNF-α (p = 0.024), MCP-1 (p = 0.008) and EGF (p = 0.0001) were improved by curcuminoids in NAFLD patients. CONCLUSIONS: The results of our study showed that curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD and this might be at least partly responsible for the anti-steatotic effects of curcuminoids.

Fault detection and isolation in the challenging Tennessee Eastman process by using image processing techniques.

The early fault detection and isolation in industrial systems is a critical factor in preventing equipment damage. In the proposed method, instead of using the time signals of sensors, the 2D image obtained by placing these signals next to each other in a matrix has been used; and then a novel fault detection and isolation procedure has been carried out based on image processing techniques. Different features including texture, wavelet transform, mean and standard deviation of the image accompanied with MLP and RBF neural networks based classifiers have been used for this purpose. Obtained results indicate the notable efficacy and success of the proposed method in detecting and isolating faults of the Tennessee Eastman benchmark process and its superiority over previous techniques.

The Yin and Yang of carbon nanomaterials in atherosclerosis.

With unique characteristics such as high surface area, capacity of various functionalization, low weight, high conductivity, thermal and chemical stability, and free radical scavenging, carbon nanomaterials (CNMs) such as carbon nanotubes (CNTs), fullerene, graphene (oxide), carbon nanohorns (CNHs), and their derivatives have increasingly been utilized in nanomedicine and biomedicine. On the one hand, owing to ever-increasing applications of CNMs in technological and industrial fields as well as presence of combustion-derived CNMs in the ambient air, the skepticism has risen over the adverse effects of CNMs on human being. The influences of CNMs on cardiovascular system and cardiovascular diseases (CVDs) such as atherosclerosis, of which consequences are ischemic heart disease and ischemic stroke, as the main causes of death, is of paramount importance. In this regard, several studies have been devoted to specify the biomedical applications and cardiovascular toxicity of CNMs. Therefore, the aim of this review is to specify the roles and applications of various CNMs in atherosclerosis, and also identify the key role playing parameters in cardiovascular toxicity of CNMs so as to be a clue for prospective deployment of CNMs.

MicroRNAs and type 2 diabetes mellitus: Molecular mechanisms and the effect of antidiabetic drug treatment.

The incidence of type 2 diabetes mellitus (T2DM), the most prevalent metabolic disease, is rapidly growing worldwide. T2DM has several underlying causes involved in its development. In recent decades, there is compelling evidence demonstrating that microRNAs (miRs) are implicated in the pathophysiology of T2DM. miRs are small non-coding RNAs which serve as endogenous gene regulators by binding to specific sequences in RNA and modifying gene expression toward up- or down-regulation. T2DM occurrence and complications may be influenced by increasing or decreasing the activity of some miRs. In the present narrative review, we comment on four molecular pathways/mechanisms that mediate the link between T2DM and different forms of miRs. These mechanisms include involvement of miRs in beta cells development, insulin sensitivity/resistance, insulin production/secretion and insulin signaling. The effects of antidiabetic drugs on miRs are also discussed.