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1.
Heliyon ; 10(7): e28053, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38560140

ABSTRACT

Background: Afamin is a hepatokine that involves in glucose and lipids metabolism. miR-122 is mainly expressed in liver and involves in lipid and carbohydrate metabolism. This study aimed at investigating the circulating afamin, its correlation with type 2 diabetes mellitus (T2DM) and miR-122 gene expression in T2DM patients and healthy control subjects according to the duration of diabetes. Methods: This case-control study included 220 participants, with 100 individuals serving as controls and 120 individuals diagnosed with type 2 diabetes mellitus (T2DM). The miR-122 gene expression was assessed using real-time PCR. The serum concentration of biochemical parameters such as glucose levels, lipid profile, and small-dense low-density lipoprotein (sdLDL) were measured using colorimetric kits. Circulating afamin and insulin levels were assayed using an ELISA kit. Glycated hemoglobin (HbA1c) was measured using capillary electrophoresis. Results: Circulating afamin level was significantly higher in T2DM patients compared to the control group, (73.8 ± 10.8 vs. 65.9 ± 8.7, respectively; P < 0.001). Similarly, miR122 expression was significantly increased in T2DM patients compared to healthy control subjects (4.24 ± 2.01 vs. 1.00 ± 0.85, respectively; P < 0.001). Among patients diagnosed with T2DM, those with longstanding diabetes (>5 years) exhibited significantly higher levels of circulating afamin and miR-122 expression compared to individuals with a shorter duration of diabetes (≤5 years) (P < 0.05). Circulating afamin levels were significantly correlated with waist circumference, small-dense low-density lipoprotein (sdLDL), fasting blood sugar (FBS), insulin, resistance to insulin, and miR-122 expression, depending on the duration of the disease (P < 0.05). Furthermore, the performance of afamin as a diagnostic marker for T2DM was confirmed through receiver operating characteristic (ROC) analysis, yielding an area under the curve (AUC) of 0.7 (P < 0.001). Conclusions: Circulating afamin involved in the T2DM-related complications and its concentration is positively correlated to the miR-122 expression, especially in patient with longstanding diabetes.

2.
Clin Chim Acta ; 556: 117829, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38355000

ABSTRACT

Glioblastoma (GBM) is the most common type of malignant brain tumor.The discovery of microRNAs and their unique properties have made them suitable tools as biomarkers for cancer diagnosis, prognosis, and evaluation of therapeutic response using different types of nanomaterials as sensitive and specific biosensors. In this review, we discuss microRNA-based electrochemical biosensing systems and the use of nanoparticles in the evolving development of microRNA-based biosensors in glioblastoma.


Subject(s)
Biosensing Techniques , Glioblastoma , MicroRNAs , Nanoparticles , Nanostructures , Humans , MicroRNAs/genetics , Glioblastoma/diagnosis , Glioblastoma/genetics , Glioblastoma/therapy , Nanostructures/chemistry , Biomarkers, Tumor/genetics , Electrochemical Techniques
3.
DNA Cell Biol ; 43(3): 108-124, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38394131

ABSTRACT

Around 50% of all occurrences of infertility are attributable to the male factor, which is a significant global public health concern. There are numerous circumstances that might interfere with spermatogenesis and cause the body to produce abnormal sperm. While evaluating sperm, the count, the speed at which they migrate, and their appearance are the three primary characteristics that are analyzed. MicroRNAs, also known as miRNAs, are present in all physiological fluids and tissues. They participate in both physiological and pathological processes. Researches have demonstrated that the expression of microRNA genes differs in infertile men. These genes regulate spermatogenesis at various stages and in several male reproductive cells. Hence, microRNAs have the potential to act as useful indicators in the diagnosis and treatment of male infertility and other diseases affecting male reproduction. Despite this, additional research is necessary to determine the precise miRNA regulation mechanisms.


Subject(s)
Infertility, Male , MicroRNAs , Humans , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Semen/metabolism , Infertility, Male/genetics , Spermatozoa/metabolism , Spermatozoa/pathology , Spermatogenesis/genetics , Fertility/genetics
4.
Clin Chim Acta ; 554: 117796, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38272250

ABSTRACT

Liver cancer is one of the deadliest types worldwide and early diagnosis is highly important for successful treatment. Therefore, it is necessary to develop rapid, sensitive, simple, and inexpensive analytical tools for its detection. MicroRNAs (miRNA) represent unique biomarkers whose expression in biofluids is strongly associated with cancer in general and miR-21, -31, -122, -145, -146a, -200c, -221, -222, and -223 in liver cancer, specifically. Various biosensors for miRNA detection have been developed. These include electrochemical biosensors based on amperometric, potentiometric, conductometric and impedimetric technology. Furthermore, the use of advanced nanomaterials with enhanced chemical stability, conductivity and electrocatalytic activity have greatly increased the sensitivity and specificity of these devices. The present review focuses on recent advances in electrochemical biosensors for miRNA detection in liver cancer.


Subject(s)
Biosensing Techniques , Liver Neoplasms , MicroRNAs , Nanostructures , Humans , MicroRNAs/genetics , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Biomarkers , Electrochemical Techniques
5.
Sci Rep ; 13(1): 14362, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37658147

ABSTRACT

Electrolytes have a wide range of technological applications. Despite the recent improvements in characterizing and predicting the phase behavior of microemulsion systems by hydrophilic-lipophilic deviation (HLD) and net-average curvature (NAC) frameworks, they are ineffective in the presence of different salts. This work seeks to bridge this gap by investigating the influence of salt nature on the microemulsion phase formulation. First, a one-dimensional salinity scan on different microemulsion systems consisting of sodium dodecyl benzene sulfonate as a surfactant, hexane as an oil and, several brines was carried out, and the effect of each salt on the phase behavior were precisely evaluated. The results for optimum salinity and solubilization parameter of different salts were consistent with the Hofmeister series. In addition, multiple linear regression model is presented to accurately predicting the optimum salinity of different salts using this research data and all the available experimental data. The results revealed that the values estimated by this model is in significant consistency with the experimental data by correlation coefficient of 0.92. Finally, the effect of salt type on the NAC parameters (length parameter, and characteristic length[Formula: see text] were evaluated to improve the predicting ability of this equation of state in the presence of various salts. We found that salt nature has a significant impact on both these parameters. It was found that the length parameter is linearly dependent on the optimum ionic strength of salts while the salting-out capacity of each salt was predominant factor affecting the characteristic length.

6.
Pharm Nanotechnol ; 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37605419

ABSTRACT

INTRODUCTION: In this study, we have investigated the aluminium phosphide (ALP) toxicity on Renal Function and oxidative stress in kidney tissue of male rats and the possible protective role of Curcumin and nanoCurcumin against ALP-induced nephrotoxicity. METHODS: Thirty-six adult male rats were divided into 6 groups (n=6). ALP (2 mg/kg oral administration) and control groups received Curcumin and nanoCurcumin (oral administration 100 mg/kg ( or without it. After seven days of treatment, kidney parameters, oxidative stress biomarkers, and expression level of sirtuins1 (SIRT1)/Forkhead box protein O1 (FoxO1) pathway genes were evaluated in kidney tissue. In addition, histopathological changes in the kidney tissues were assayed. RESULTS: In the ALP group, compared to the control group, lipid peroxidation levels, urea, and creatinine were increased, and total antioxidant capacity and thiol groups decreased significantly P<0.05. In Curcumin and nanoCurcumin groups compared to the ALP group, lipid peroxidation and creatinine decreased significantly P<0.05. Also, Curcumin and nanoCurcumin improved the tissue damage caused by ALP. NanoCurcumin modulated the effect of ALP on the gene expression levels in SIRT1/FoxO1. CONCLUSION: The present study showed that ALP intoxication in kidney tissue can induce oxidative damage. Moreover, Curcumin and nanocurcumin, as potential antioxidants, can be effective therapeutics in ALP-induced nephrotoxicity.

7.
CNS Neurosci Ther ; 29(11): 3150-3159, 2023 11.
Article in English | MEDLINE | ID: mdl-37452477

ABSTRACT

Epilepsy is a common chronic neurological disorder caused by aberrant neuronal electrical activity. Antiseizure medications (ASMs) are the first line of treatment for people with epilepsy (PWE). However, their effectiveness may be limited by their inability to cross the blood-brain barrier (BBB), among many other potential underpinnings for drug resistance in epilepsy. Therefore, there is a need to overcome this issue and, hopefully, improve the effectiveness of ASMs. Recently, synthetic nanoparticle-based drug delivery systems have received attention for improving the effectiveness of ASMs due to their ability to cross the BBB. Furthermore, exosomes have emerged as a promising generation of drug delivery systems because of their potential benefits over synthetic nanoparticles. In this narrative review, we focus on various synthetic nanoparticles that have been studied to deliver ASMs. Furthermore, the benefits and limitations of each nano-delivery system have been discussed. Finally, we discuss exosomes as potentially promising delivery tools for treating epilepsy.


Subject(s)
Epilepsy , Exosomes , Humans , Epilepsy/drug therapy , Blood-Brain Barrier , Drug Delivery Systems , Anticonvulsants/therapeutic use
8.
AIMS Neurosci ; 10(1): 56-74, 2023.
Article in English | MEDLINE | ID: mdl-37077959

ABSTRACT

Aluminum phosphide (ALP) is among the most significant causes of brain toxicity and death in many countries. Curcumin (CUR), a major turmeric component, is a potent protective agent against many diseases, including brain toxicity. This study aimed to examine the probable protection potential of nanomicelle curcumin (nanomicelle-CUR) and its underlying mechanism in a rat model of ALP-induced brain toxicity. A total of 36 Wistar rats were randomly divided into six groups (n = 6) and exposed to ALP (2 mg/kg/day, orally) + CUR or nanomicelle-CUR (100 mg/kg/day, orally) for 7 days. Then, they were anesthetized, and brain tissue samples were dissected to evaluate histopathological alterations, oxidative stress biomarkers, gene expression of SIRT1, FOXO1a, FOXO3a, CAT and GPX in brain tissue via hematoxylin and eosin (H&E) staining, biochemical and enzyme-linked immunosorbent assay (ELISA) methods and Real-Time PCR analysis. CUR and nanomicelle-CUR caused significant improvement in ALP-induced brain damage by reducing the MDA levels and induction of antioxidant capacity (TTG, TAC and SOD levels) and antioxidant enzymes (CAT, GPX), modulation of histopathological changes and up-regulation of gene expression of SIRT1 in brain tissue. It was concluded that nanomicelle-CUR treatment ameliorated the harmful effects of ALP-induced brain toxicity by reducing oxidative stress. Therefore, it could be considered a suitable therapeutic choice for ALP poisoning.

9.
Mol Biol Rep ; 50(5): 4217-4224, 2023 May.
Article in English | MEDLINE | ID: mdl-36899278

ABSTRACT

BACKGROUND: miR-122 is a liver specific micro-RNA that participates in the regulation of carbohydrate and lipid metabolism. The rs17669 variant of miR-122 is positioned at the flanking region of miR-122 and may affect its stability and maturation. Therefore, this study was aimed to investigate the association of the rs17669 polymorphism with the miR-122 circulating level, risk of type 2 diabetes mellitus (T2DM) development, and biochemical parameters in T2DM patients and matched healthy controls. METHODS AND RESULTS: This study involved 295 subjects (controls: n = 145 and T2DM: n = 150). The rs17669 variant genotyping was done by ARMS-PCR. Serum biochemical parameters including lipid profile, small-dense low density lipoprotein (sdLDL) and glucose were measured by colorimetric kits. Insulin and Glycated hemoglobin (HbA1c) were assayed using ELISA and capillary electrophoresis methods, respectively. miR-122 expression was measured by real-time PCR. There was no significant difference between study groups in terms of allele and genotype distribution (P > 0.05). The rs17669 variant did not have any significant association with miR-122 gene expression and biochemical parameters (P > 0.05). miR-122 expression level in T2DM patients was significantly higher than that in control subjects (5.7 ± 2.4 vs. 1.4 ± 0.78) (P < 0.001). Furthermore, miR-122 fold change had a positive and significant correlation with low-density lipoprotein cholesterol (LDL-C), sdLDL, fasting blood sugar (FBS), and insulin resistance (P < 0.05). CONCLUSION: It can be concluded that the rs17669 variant of miR-122 is not associated with the miR-122 expression and T2DM-associated serum parameters. Furthermore, it can be suggested that miR-122 dysregulation is involved in T2DM development through inducing dyslipidemia, hyperglycemia, and resistance to insulin.


Subject(s)
Diabetes Mellitus, Type 2 , Dyslipidemias , Hyperglycemia , MicroRNAs , Humans , Hyperglycemia/genetics , MicroRNAs/genetics , Insulin , Lipoproteins, LDL , Dyslipidemias/genetics , Blood Glucose/metabolism
10.
Clin Chim Acta ; 541: 117245, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36754191

ABSTRACT

Gastrointestinal (GI) cancers are one of the most common causes of cancer-related mortality. The discovery of microRNAs (miRs) and their unique role in cancer and other diseases has prompted the development of highly sensitive molecular diagnostic tools using nanomaterials as sensitive and specific biosensors. Among these, electrochemical biosensors, which are based on a simple and inexpensive design, make them desirable in clinical applications as well as a mass-produced point-of-care device. We review miR-based electrochemical biosensors in GI cancer and examine the use of nanoparticles in the evolving development of miR-based biosensors. Among these, a number of approaches including redox labeled probes, catalysts, redox intercalating agents and free redox indicators are highlighted for use in electrochemical biosensor technology.


Subject(s)
Biosensing Techniques , Gastrointestinal Neoplasms , MicroRNAs , Nanostructures , Humans , Nanostructures/chemistry , Nanotechnology , Electrochemical Techniques
11.
Biotechnol Appl Biochem ; 70(1): 318-329, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35484728

ABSTRACT

Testosterone is an anabolic steroid and a major sex hormone in males. It plays vital roles, including developing the testis, penis, and prostate, increasing muscle and bone, and sperm production. In both men and women, testosterone levels should be in normal ranges. Besides, testosterone and its analogs are major global contributors to doping in sport. Due to the importance of testosterone testing, novel, accurate biosensors have been developed. This review summarizes the various methods for testosterone measurement. Also, recent optical and electrochemical approaches for the detection of testosterone and its analogs have been discussed.


Subject(s)
Biosensing Techniques , Semen , Humans , Male , Female , Testosterone
12.
Rep Biochem Mol Biol ; 12(3): 448-457, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38618258

ABSTRACT

Background: Recent studies have implicated dysregulated long non-coding RNA (lncRNA) levels in the pathogenesis of type 2 diabetes (T2D). This study aimed to assess the expression of circulating HOTAIR and uc.48+, examining their correlation with clinical and biochemical variables in T2D patients, pre-diabetic individuals, and healthy controls. Methods: Peripheral blood levels of lncRNAs were quantified using QRT-PCR in 65 T2D patients, 63 pre-diabetic individuals, and 63 healthy subjects. Pathway enrichment analysis was conducted to explore the functional enrichment of lncRNA-miRNA targets. Results: Analysis revealed a significantly elevated circulating level of HOTAIR in both T2D (P < 0.0001) and pre-diabetic patients (P = 0.04) compared to controls. ROC analysis demonstrated that, at a cutoff value of 9.1, with a sensitivity of 80% and specificity of 62%, HOTAIR could distinguish T2D patients from controls (AUC = 0.723, 95% CI 0.637-0.799, P < 0.0001). Spearman correlation analysis identified a significant positive correlation between HOTAIR expression, HbA1c, and insulin resistance (P < 0.005). MiRNA enrichment analysis indicated significant enrichment of diabetes-related pathways among HOTAIR's miRNA targets. Conversely, no significant difference in uc.48+ circulating levels between groups was observed, but a significant positive correlation emerged between uc.48+ and systolic blood pressure. Conclusions: This study provides evidence that elevated HOTAIR expression levels are associated with T2D progression, suggesting their potential as biomarkers for early diagnosis and prognosis.

13.
Clin Chim Acta ; 551: 117618, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-38375624

ABSTRACT

The term "gynecologic cancer" pertains to neoplasms impacting the reproductive tissues and organs of women encompassing the endometrium, vagina, cervix, uterus, vulva, and ovaries. The progression of gynecologic cancer is linked to various molecular mechanisms. Historically, cancer research primarily focused on protein-coding genes. However, recent years have unveiled the involvement of non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs (LncRNAs), and circular RNAs, in modulating cellular functions within gynecological cancer. Substantial evidence suggests that ncRNAs may wield a dual role in gynecological cancer, acting as either oncogenic or tumor-suppressive agents. Numerous clinical trials are presently investigating the roles of ncRNAs as biomarkers and therapeutic agents. These endeavors may introduce a fresh perspective on the diagnosis and treatment of gynecological cancer. In this overview, we highlight some of the ncRNAs associated with gynecological cancers.


Subject(s)
Gynecology , MicroRNAs , Neoplasms , RNA, Long Noncoding , Humans , Female , RNA, Untranslated/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Neoplasms/drug therapy
14.
Clin Chim Acta ; 537: 127-132, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36330945

ABSTRACT

Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of mortality among men. The recurrent reports of false-positive results of common PCa biomarkers have led to the introduction of some promising biomarkers for PCa, such as exosomal non-coding RNAs (ncRNAs). Exosomes contain various components, such as several ncRNAs (miRNAs and lncRNAs), which are important in the initiation and progression of PCa. These ncRNAs also reflect the state of the origin cell. In this article, we reviewed research on the importance and roles of ncRNAs in PCa, focusing on exosomal ncRNAs. We highlighted plasma exosomal miRNAs (8 miRNAs), urine exosomal miRNAs (19miRNAs), serum miRNAs (2 miRNAs), and five miRNAs in semen used for PCa diagnosis. Also, four exosomal lncRNAs in plasma and urine can be used as biomarkers for PCa diagnosis.


Subject(s)
Exosomes , MicroRNAs , Prostatic Neoplasms , RNA, Long Noncoding , Male , Humans , Biomarkers, Tumor/genetics , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Exosomes/genetics , RNA, Untranslated
15.
Biomed Res Int ; 2022: 7659765, 2022.
Article in English | MEDLINE | ID: mdl-36132078

ABSTRACT

Background: The present study aimed to evaluate the effect of nanocurcumin and curcumin on liver transaminases, lipid profile, oxidant and antioxidant system, and pathophysiological changes in aluminium phosphide (ALP) induced hepatoxicity. Material and Methods. In this experimental study, thirty-six male Wistar rats were randomly divided into six groups curcumin (Cur), nanocurcumin (Nanocur), ALP, ALP+Cur, and ALP+Nanocur. All treatments were performed by oral gavage for seven days. After treatment, animals were sacrificed, and liver and blood samples were taken. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), total bilirubin, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were measured by photometric methods. Total antioxidant capacity (TAC) and malondialdehyde (MDA) as parameters of oxidative stress and mRNA expression of the nonenzyme protein including Sirtuin 1 (STR1), Forkhead box protein O1 (FOXO1) and protein O3 (FOXO3), catalase (CAT), and glutathione peroxidase (GPX) as the enzyme protein in homogenized tissues have been investigated. A histologist analyzed liver tissue sections after staining with hematoxylin-eosin. Results: In the aluminium phosphide group, there was a significant increase in MDA, ALT, AST, and AP and total bilirubin, cholesterol, triglyceride, LDL, and VLDL; AST, ALT, total bilirubin, LDL, VLDL, cholesterol, and MDA were significantly decreased; and HDL and TAC were significantly increased compared to ALP (P < 0.05). In the ALP+Nanocur group, ALT, AST, ALP, total bilirubin, cholesterol, LDL, VLDL, triglyceride, and MDA were significantly decreased and HDL and TAC were increased significantly (P < 0.05). The effect of nanocurcumin on controlling serum levels of LDL, VLDL, triglyceride, and MDA in ALP-poisoned rats was significantly more than curcumin (P < 0.05). The ALP group had significant changes in genes SIRT1, FOXO1a, FOXO3a, CAT, and GPX compared to healthy controls (P < 0.05). Nanocurcumin mice expressed more SIRT1, FOXO1a, CAT, and GPX genes than controls, and curcumin-treated mice expressed more SIRT1 and FOXO1a genes (P < 0.05). Histopathological findings also indicated a more significant protective effect of nanocurcumin relative to curcumin against ALP-induced hepatotoxicity. Conclusion: Nanocurcumin significantly protects the liver against aluminum phosphide toxicity. It is suggested that nanocurcumin-based drugs be developed to reduce the toxic effects of ALP in poisoned patients.


Subject(s)
Antioxidants , Curcumin , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Aluminum Compounds , Animals , Antioxidants/pharmacology , Aspartate Aminotransferases , Bilirubin/metabolism , Catalase/metabolism , Cholesterol, LDL/metabolism , Curcumin/metabolism , Curcumin/pharmacology , Eosine Yellowish-(YS)/metabolism , Forkhead Box Protein O1/metabolism , Glutathione Peroxidase/metabolism , Hematoxylin/metabolism , Lipoproteins, HDL , Lipoproteins, VLDL/metabolism , Lipoproteins, VLDL/pharmacology , Liver/pathology , Male , Malondialdehyde/metabolism , Mice , Oxidants/metabolism , Oxidative Stress , Phosphines , RNA, Messenger/metabolism , Rats , Rats, Wistar , Sirtuin 1/metabolism , Triglycerides/metabolism
16.
Cell Biochem Funct ; 40(3): 232-247, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35258097

ABSTRACT

Traumatic brain injury (TBI) is one of the most concerning health issues in which the normal brain function may be disrupted as a result of a blow, bump, or jolt to the head. Loss of consciousness, amnesia, focal neurological defects, alteration in mental state, and destructive diseases of the nervous system such as cognitive impairment, Parkinson's, and Alzheimer's disease. Parkinson's disease is a chronic progressive neurodegenerative disorder, characterized by the early loss of striatal dopaminergic neurons. TBI is a major risk factor for Parkinson's disease. Existing therapeutic approaches have not been often effective, indicating the necessity of discovering more efficient therapeutic targets. The mammalian target of rapamycin (mTOR) signaling pathway responds to different environmental cues to modulate a large number of cellular processes such as cell proliferation, survival, protein synthesis, autophagy, and cell metabolism. Moreover, mTOR has been reported to affect the regeneration of the injured nerves throughout the central nervous system (CNS). In this context, recent evaluations have revealed that mTOR inhibitors could be potential targets to defeat a group of neurological disorders, and thus, a number of clinical trials are investigating their efficacy in treating dementia, autism, epilepsy, stroke, and brain injury, as irritating neurological defects. The current review describes the interplay between mTOR signaling and major CNS-related disorders (esp. neurodegenerative diseases), as well as the mTOR signaling-TBI relationship. It also aims to discuss the promising therapeutic capacities of mTOR inhibitors during the TBI.


Subject(s)
Brain Injuries, Traumatic , Central Nervous System Diseases , Neurodegenerative Diseases , Parkinson Disease , Brain Injuries, Traumatic/drug therapy , Humans , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
17.
J Cell Physiol ; 237(4): 2095-2106, 2022 04.
Article in English | MEDLINE | ID: mdl-35128660

ABSTRACT

Lung cancer therapeutic resistance, especially chemoresistance, is a key issue in the management of this malignancy. Despite the development of novel molecularly targeted drugs to promote therapeutic efficacy, 5-year survival of lung cancer patients is still dismal. Molecular studies through the recent years have fortunately presented multiple genes and signaling pathways, which contribute to lung cancer chemoresistance, providing a better perception of the biology of tumor cells, as well as the molecular mechanisms involved in their resistance to chemotherapeutic agents. Among those mechanisms, transfer of extracellular vesicles, such as exosomes, between cancer cells and the surrounding noncancerous ones is considered as an emerging route. Exosomes can desirably function as signaling vesicles to transmit multiple molecules from normal cells to cancer cells and their microenvironment, or vice versa. Using this ability, exosomes may affect the cancer cells' chemoresistance/chemosensitivity. Recently, noncoding RNAs (esp. microRNAs and long noncoding RNAs), as key molecules transferred by exosomes, have been reported to play a substantial role in the process of drug resistance, through modulation of various proteins and their corresponding genes. Accordingly, the current review principally aims to highlight exosomal micro- and long noncoding RNAs involved in lung cancer chemoresistance. Moreover, major molecular mechanisms, which connect corresponding RNA molecules to drug resistance, will briefly be addressed, for better clarifying of possible roles of exosomal noncoding RNAs in promoting the effectiveness of lung cancer therapy.


Subject(s)
Exosomes , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Drug Resistance, Neoplasm/genetics , Exosomes/metabolism , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Untranslated/metabolism , Tumor Microenvironment/genetics
18.
Biotechnol Appl Biochem ; 69(6): 2658-2672, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34997643

ABSTRACT

Laccase belongs to the polyphenol oxidase family and is very important in removing environmental pollutants due to its structural and functional properties. Recently, the ability of laccase to oxidize phenolic and nonphenolic substances has been considered by many researchers. This enzyme's application scope includes a broad range of chemical processes and industrial usages, such as bioremediation, nanobiotechnology, woodworking industries, bleaching of paper pulp, dyeing in the textile industry, biotechnological uses in food industries, biorefining, detoxification from wastewater, production of organic matter from phenolic and amine substrates, and biofuels. Although filamentous fungi produce large amounts of laccase, high-yield industrial-scale production of laccase is still faced with many problems. At present, researchers are trying to increase the efficiency and productivity and reduce the final price of laccase by finding suitable microorganisms and improving the process of production and purification of laccase. This article reviews the introduction of laccase, its properties, production processes, and the effect of various factors on the enzyme's stability and activity, and some of its applications in various industries.


Subject(s)
Environmental Pollutants , Laccase , Laccase/chemistry , Biotechnology , Fungi , Biodegradation, Environmental
19.
J Recept Signal Transduct Res ; 42(5): 429-438, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34645362

ABSTRACT

PURPOSE: Doxorubicin (DOX) is a common chemotherapeutic agent, with toxic side effects, and chemoresistance. Combination chemotherapy is a successful approach to overcome these limitations. Here, we investigated the effects of pioglitazone (PGZ), a PPARγ agonist, and/or DOX on the viability, cell cycle, apoptosis on THP-1 cells and normal human monocytes (NHMs). METHODS: MTT assay was used to evaluate the cytotoxicity of DOX and/or PGZ. Cell cycle progression and apoptosis induction were examined by PI or Annexin V-PI double staining, and analyzed by flow cytometry. Quantitative RT-PCR was used to evaluate the changes in the mRNA expression of cell cycle progression or apoptosis-associated genes including P27, P21, CDK2, P53, BCL2 and FasR. RESULTS: DOX, PGZ and DOX + PGZ exerted their cytotoxic effects in a dose- and time-dependent manner with low toxicity on NHMs. The cell growth inhibitory effects of DOX were in association with G2/M arrest, while PGZ executed S phase arrest. PGZ treatment enhanced G2/M among DOX-treated combinations with moderate elevation in the S phase. DOX, PGZ and combined treatments induced apoptosis (mostly late phase) in a dose-dependent manner. All treatments resulted in the significant overexpression of p21, p27, p53 and FasR genes and downregulation of CDK2. DOX + PGZ combined treatments exhibited the most significant changes in mRNA expression. CONCLUSION: We demonstrated that the antiproliferative, cell cycle regulation and apoptosis-inducing capacity of DOX was enhanced by PGZ in THP-1 leukemia cells in a dose-dependent manner. Therefore, the combination of DOX + PGZ could be used as a novel combination to target AML.


Subject(s)
Antineoplastic Agents , Leukemia , Annexin A5/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis , Cell Cycle , Cell Cycle Checkpoints , Cell Line, Tumor , Doxorubicin/pharmacology , G2 Phase Cell Cycle Checkpoints , Humans , Monocytes , PPAR gamma/genetics , PPAR gamma/metabolism , Pioglitazone/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger , THP-1 Cells , Tumor Suppressor Protein p53
20.
Drug Res (Stuttg) ; 72(2): 100-108, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34614532

ABSTRACT

OBJECTIVE: Aluminum phosphide (AlP) is widely used to protect stored food products and grains from pests and rodents. The availability of AlP, especially in Asian countries it has become a desirable factor to commit suicide. The phosphine produced from ALP is a very reactive radical and a respiratory inhibitor that causes oxidative damage. There is no dedicated antidote or effective drug to manage AlP-induced lung toxicity. The present study aims to evaluate and compare the protective effects of curcumin and nanocurcumin on ALP­induced subacute lung injury and determine the underlying mechanism. METHODS: Rats were exposed to AlP (2 mg/kg/day, orally)+curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and lung tissues were collected. Oxidative stress biomarkers, genes expression of antioxidant enzymes, participated genes in the SIRT1/FOXO3 pathway, and lung histopathology were assessed by biochemical and ELISA methods, Real-Time PCR analysis, and H&E staining. RESULTS: Curcumin and nanocurcumin produced a remarkable improvement in AlP-induced lung damage through reduction of MDA, induction of antioxidant capacity (TAC, TTG) and antioxidant enzymes (CAT, GPx), modulation of histopathological changes, and up-regulation of genes expression of SIRT1, FOXO3, FOXO1 in lung tissue. CONCLUSION: Nanocurcumin had a significantly more protective effect than curcumin to prevent AlP-induced lung injury via inhibition of oxidative stress. Nanocurcumin could be considered a suitable therapeutic choice for AlP poisoning.


Subject(s)
Curcumin , Lung Injury , Aluminum Compounds , Animals , Curcumin/pharmacology , Oxidative Stress , Phosphines , Rats , Sirtuin 1
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