Sources, Degradation, Ingestion and Effects of Microplastics on Humans: A Review.

Celluloid, the predecessor to plastic, was synthesized in 1869, and due to technological advancements, plastic products appear to be ubiquitous in daily life. The massive production, rampant usage, and inadequate disposal of plastic products have led to severe environmental pollution. Consequently, reducing the employment of plastic has emerged as a pressing concern for governments globally. This review explores microplastics, including their origins, absorption, and harmful effects on the environment and humans. Several methods exist for breaking down plastics, including thermal, mechanical, light, catalytic, and biological processes. Despite these methods, microplastics (MPs, between 1 and 5 mm in size) continue to be produced during degradation. Acknowledging the significant threat that MPs pose to the environment and human health is imperative. This form of pollution is pervasive in the air and food and infiltrates our bodies through ingestion, inhalation, or skin contact. It is essential to assess the potential hazards that MPs can introduce. There is evidence suggesting that MPs may have negative impacts on different areas of human health. These include the respiratory, gastrointestinal, immune, nervous, and reproductive systems, the liver and organs, the skin, and even the placenta and placental barrier. It is encouraging to see that most of the countries have taken steps to regulate plastic particles. These measures aim to reduce plastic usage, which is essential today. At the same time, this review summarizes the degradation mechanism of plastics, their impact on human health, and plastic reduction policies worldwide. It provides valuable information for future research on MPs and regulatory development.

Ergosterol peroxide: an effect-directed detecting method from Anoectochilus elwesii and evaluation of anticancer activity.

Ergosterol peroxide (EP) in Anoectochilus elwesii possesses antioxidant and anticancer properties, yet few studies have been focused on its mechanisms and directed detecting. By practicing HPTLC-DPPH coupled with UHPLC-ESI-TOF MS, EP was located and the cytotoxic activity of EP was performed by MTT method. The apoptosis studies were conducted on SGC-7901cells by AO/EB and Annex V/PI staining method, PI flow cytometric assay, reactive oxygen species detection and mitochondrial membrane potential assay. An effect-directed detecting method of HPTLC-DPPH/UHPLC/ESI-TOF-MS was developed for EP rapidly and precisely, providing an option for identifying oxidative compounds. EP exhibits high cytotoxic activity against SGC-7901 gastric cancer cells and the morphological apoptosis suggested that EP induced apoptosis and cell cycle arrest in G0/G1 phase. It could enhance the ROS level and cause a decrease in the mitochondrial membrane potential. Its antiproliferative mechanism is G0/G1 phase arrest and might be traced through ROS-mediated mitochondrial dysfunction pathways.

Ameliorating effect on glycolipid metabolism and chemical profile of Millettia speciosa champ. extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Millettia speciosa Champ., also called Niu dali, is a fabaceous medicinal plant mainly distributed in southeast China, where it is a functional food for developing physical strength, and often used traditionally in medicinal treatment of numbness of the wrists, diabetes, hepatitis, and so on. AIM OF THE STUDY: To investigate the chemical profile, ameliorating effects of MSC on glycolipid metabolism in diabetic mice and to identify the possible mechanism of action. MATERIALS AND METHODS: High-performance liquid chromatography coupled with electrospray ionization quadrupole time of flight mass spectrometry (HPLC-ESI-QTOF-MS) was applied to analyze the chemical compositions from M. speciosa extract (MSC). MSC was orally administered to high-fat diet and STZ-induced diabetic mice at doses of 4.55, 9.10 and 13.65 mg/(kg·d) respectively for 10 weeks. Indices of glycolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI), blood lipids, HPA-axis hormones, and related gene expressions were evaluated. RESULTS: 86 compounds were tentatively identified from MSC, counting for 91.97% of the total extract, mainly including 23 alkaloids (including 2 cyanogenetic glycosides firstly identified in this species, total content accounted to 39.71%), 23 flavonoids (11.91%), 17 acids (including 3 amino acids, 9 phenolic acids and 5 organic acids; 9.2%), 9 terpenoids and steroids (20.13%), 7 esters (3.33%), 3 lignans (3.73%), 3 saccharides (4.0%) and 1 anthraquinone (0.18%). MSC could ameliorate the glycolipid disorder in diabetic mice markedly, and significant regulations on CRH and ACTH hormones were observed. Moreover, the cellular morphology of liver and pancreas were significantly improved and the expressions of IRS2, PI3K, Akt and GLUT4 were significantly up-regulated by MSC treatment. CONCLUSION: This was the first time to study the chemical profile and ameliorating effect on glycolipid metabolism of M. speciosa. It was found to be rich in flavonoids and alkaloids, which might support the potential relation of material foundation and the activity in regulating glycolipid metabolism. The ameliorating effect on glycolipid disorder in diabetic mice might be associated to the regulation of related hormones of the HPA axis and the IRS2/PI3K/Akt/GLUT4 signalling pathway. It was of great significance for advanced directed separation and pharmacological activity research of MSC.

Comprehensive chemical analysis of Zhenshu Tiaozhi formula and its effect on ameliorating glucolipid metabolic disorders in diabetic rats.

The present study aims to reveal the compositions of Zhenshu TiaoZhi formula (FTZ) comprehensively, and investigate whether FTZ ameliorate glucolipid metabolism disorders in diabetic rats with the involvement of glucocorticoids in peripheral insulin-sensitive tissues. The fingerprint was established based on 11 batches of FTZ samples and chemical compostions of FTZ were identified by ultra performance liquid chromatography-time of flight/mass spectrometry (UPLC-TOF/MS). High-fat diet (HFD) and streptozotocin (STZ) induced diabetic rats were orally administrated with 3 and 6 g/kg body weight of FTZ for 8 weeks. Indices of glucolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI) and blood lipids were evaluated after treatment of FTZ. The levels of HPA axis hormones were examined. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to investigate the relative mRNA expressions of 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) and glucolipid metabolic indicators. A reference fingerprint was established and 93 compounds of FTZ were tentatively identified. In vivo, FTZ treatment exerted antidiabetic and antidyslipidemic effects while decreased the level of corticotropin releasing hormone (CRH). 11ß-HSD1 mRNA showed similar trajectory in both liver, adipose and skeletal muscle tissues, which was up-regulated in diabetic group and ameliorated in FTZ groups. Furthermore, the expressions of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and adipose triglyceride lipase (ATGL) were down-regulated in liver and skeletal muscle. These results elucidated the compositions of FTZ comprehensively and indicated its effect on ameliorating glucolipid metabolism of diabetic rats involved hypothalamus-pituitary-adrenal (HPA) axis homeostasis. Down-regulating 11ß-HSD1 in insulin-sensitive tissues might be a potential mechanism of FTZ in treating type 2 diabetes mellitus (T2DM).

Hypothalamus-pituitary-adrenal Axis in Glucolipid metabolic disorders.

With the change of life style, glucolipid metabolic disorders (GLMD) has become one of the major chronic disorders causing public health and clinical problems worldwide. Previous studies on GLMD pay more attention to peripheral tissues. In fact, the central nervous system (CNS) plays an important role in controlling the overall metabolic balance. With the development of technology and the in-depth understanding of the CNS, the relationship between neuro-endocrine-immunoregulatory (NEI) network and metabolism had been gradually illustrated. As the hub of NEI network, hypothalamus-pituitary-adrenal (HPA) axis is important for maintaining the balance of internal environment in the body. The relationship between HPA axis and GLMD needs to be further studied. This review focuses on the role of HPA axis in GLMD and reviews the research progress on drugs for GLMD, with the hope to provide the direction for exploring new drugs to treat GLMD by taking the HPA axis as the target and improve the level of prevention and control of GLMD.

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction.

OBJECTIVES: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). METHODS: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. RESULTS: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. CONCLUSION: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization.

The aim of the present study was to investigate whether low-frequency ultrasound (US)-mediated microvessel disruption combined with docetaxel (DTX) can be used as a novel type of chemoembolization. Mice were assigned to four groups: i) The USMB group, treated with low-frequency US combined with microbubbles (USMB); ii) the DTX group, treated with DTX; iii) the USMB + DTX group, treated with combined therapy; and iv) the control group, which was untreated. Immediately after the first treatment, the average peak intensity (API) on contrast-enhanced US was calculated, and tumors were excised for hematoxylin and eosin (HE) staining. At 2 weeks post-treatment, the tumor volumes and wet weights were calculated, and tumors were excised for immunohistochemistry to calculate apoptotic index (AI), proliferative index (PI) and microvessel density (MVD) values. Immediately after the first treatment, in the DTX and control groups, the tumors demonstrated abundant perfusion enhancement, while in the USMB + DTX and USMB groups, blood perfusion of the tumors was interrupted. Compared with that of the control group, the API was significantly lower in the USMB + DTX USMB groups (all P<0.001). HE staining showed that tumor microvasculature was disrupted into flaky hematomas and severely dilated microvessels in the USMB + DTX and USMB groups. In the DTX and control groups, there was no distinct evidence of the disruption and dilation of blood microvessels. At the end of the treatment, the mean tumor inhibition ratio was 73.33, 46.67 and 33.33% for the USMB + DTX, DTX and USMB groups, respectively. The USMB + DTX group had the highest AI, and the lowest PI and MVD compared with the other groups, although the difference between the USMB + DTX and DTX groups with regard to PI and MVD was not significant (USMB + DTX vs. DTX group, P=0.345 and P=0.059, respectively). In conclusion, as a novel type of chemoembolization, USMB combined with DTX is more effective than USMB or DTX alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis.

[MicroRNA-182 modulates high glucose-induced cardiomyocyte hypertrophy via targeting Rac1].

OBJECTIVE: To investigate the role and signalling of microRNA(miR)-182 on regulating high glucose-induced cardiomyocyte hypertrophy. METHODS: The candidates of miR which might potentially be involved on targeting Rac1 were predicted by applying bioinformatics analysis. The expression of all related candidates miRs was verified by real-time reverse transcription-PCR (RT-PCR) in cardiac tissues of db/db mice and db/m mice. Then the relationship between candidates miR and Rac1 was investigated with Pearson relevant analysis. Neonatal mice cardiomyocytes were cultured and divided into 2 groups: normal glucose group and high glucose group. The level of selected miR and Rac1 in two groups was detected by RT-PCR. Neonatal mice cardiomyocytes were then randomly divided into 4 groups: normal glucose group, selected microRNA mimics control group, high glucose group, high glucose plus selected miR mimics control group. The morphology of cardiomyocyte in each group was detected under light microscope. Furthermore, Rac1, ß-MHC and α-SMA expressions were detected in cultured cardiomyocyte treated by high glucose for 48 h after transfecting selected miR mimics by RT-PCR and Western blot. RESULTS: A total of 6 miR candidates potentially targeting Rac1 were screened by bioinformatics, which were miR-182, miR-142-3p, miR-140, miR-101a, miR-429 and miR-200b. Among these candidates, miR-182 and miR-142-3p expression was significantly downregulated in cardiac tissues of db/db mice compared with db/m controls (P < 0.05). MiR-182 was negatively correlated with Rac1 by person analysis (r = -0.891 02). Downregulation of miR-182 and upregulation of Rac1, ß-MHC, α-SMA were found in high glucose-induced cardiomyocyte. After transfection of miR-182 mimics, hypertrophic changes were significantly reduced and Rac1 as well ß-MHC expression was significantly downregulated in cardiomyocyte incubated with high glucose. CONCLUSION: MiR-182 might be involved in the regulation of high glucose-induced myocardial hypertrophy process via targeting Rac1.

Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design.

The present study aimed to provide a complete exploration of the effect of sound intensity, frequency, duty cycle, microbubble volume and irradiation time on low-frequency low-intensity ultrasound (US)-mediated microvessel disruption, and to identify an optimal combination of the five factors that maximize the blockage effect. An orthogonal experimental design approach was used. Enhanced US imaging and acoustic quantification were performed to assess tumor blood perfusion. In the confirmatory test, in addition to acoustic quantification, the specimens of the tumor were stained with hematoxylin and eosin and observed using light microscopy. The results revealed that sound intensity, frequency, duty cycle, microbubble volume and irradiation time had a significant effect on the average peak intensity (API). The extent of the impact of the variables on the API was in the following order: Sound intensity; frequency; duty cycle; microbubble volume; and irradiation time. The optimum conditions were found to be as follows: Sound intensity, 1.00 W/cm2; frequency, 20 Hz; duty cycle, 40%; microbubble volume, 0.20 ml; and irradiation time, 3 min. In the confirmatory test, the API was 19.97±2.66 immediately subsequent to treatment, and histological examination revealed signs of tumor blood vessel injury in the optimum parameter combination group. In conclusion, the Taguchi L18 (3)6 orthogonal array design was successfully applied for determining the optimal parameter combination of API following treatment. Under the optimum orthogonal design condition, a minimum API of 19.97±2.66 subsequent to low-frequency and low-intensity mediated blood perfusion blockage was obtained.

Inhibitory effects of subcutaneous tumors in nude mice mediated by low-frequency ultrasound and microbubbles.

The aim of the present study was to investigate the sonication effects of 21-kHz ultrasound (US) with microbubbles (MBs) on the subcutaneous prostate tumors of nude mice. In total, 15 tumor-bearing nude mice were divided into three groups: The control group, the low-frequency US group and the US+MB group. The MBs used were from US contrast agent SonoVue. The parameters of the US were as follows: 21 kHz, 26 mW/cm2 and a 40% duty cycle (2 sec on, 3 sec off) for 3 min, once every other day for 2 weeks. Color Doppler flow imaging, hematoxylin and eosin (HE) staining, immunoblotting and transmission electron microscopy (TEM) were used to evaluate the results. Following 2 weeks of treatment, the blood flow signal disappeared in the US+MB group only, and the tumor size was smaller when compared with the control and US groups. For the immunoblotting, the intensity of cyclooxygenase-2 and vascular endothelial growth factor in the US+MB group was lower compared with the other two groups. Tumor necrosis was present and the nucleus disappeared upon HE staining in the US+MB group. Upon TEM analysis, increased cytoplasmic vacuolation and dilatation of the perinuclear cisternae of the tumor cells were found in the US+MB group. In the control and US groups, the tumors had intact vascular endothelia and vessel lumens. However, lumen occlusion of the vessels was observed in the US+MB group. In conclusion, 21-kHz low-intensity US with MBs may result in vessel occlusion and growth inhibitory effects in the subcutaneous tumors of nude mice.

Effects of low-frequency ultrasound combined with microbubbles on benign prostate hyperplasia.

INTRODUCTION: Our objective is to assess the effects of low-frequency ultrasound combined with microbubbles on benign prostate hyperplasia (BPH). METHODS: Sixteen Beagle dogs with BPH were randomly assigned into 4 groups (n = 4): control group (without treatment), G1 group (injection with 2 mL of microbubble contrast agent); G2 group (21 kHz ultrasound); and G3 group (injection with 2 mL of micro-bubble contrast agent +21 kHz ultrasound). The histopathological damage to prostate cells was assessed via transmission electron microscopy and optical microscopy. The protein expressions of prostate-specific antigen (PSA), inducible nitric oxide synthase (iNOS), superoxide dismutase (SOD) of vessels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Histopathologically, the prostate cells exhibited nuclear chromatin contraction, mitochondrial swelling, degranulation of rough endoplasmic reticulum, basement membrane rupture and cell apoptosis in the G2 and G3 groups; it was especially obvious in the G3 group, while no changes were observed in the control and G1 groups. Although prostate volume using imaging was not significantly changed in all groups after treatment, PSA was significantly reduced in the G2 and G3 groups, and especially obvious in the G3 group (p < 0.05). The iNOS and SOD, which are important oxidative stress factors, significantly increased after treatment in the G2 and G3 groups, but not in the control and G1 groups (p < 0.05). CONCLUSIONS: Low-frequency ultrasound is effective in treating BPH; low-frequency ultrasound combined with microbubbles improves the treatment efficacy.

Effects of low-frequency ultrasound and microbubbles on angiogenesis-associated proteins in subcutaneous tumors of nude mice.

It has been shown that 1 and 3 MHz low-intensity ultrasound was able to affect the fragile and leaky angiogenic blood vessels in a tumor. However, the biological effects of 21 kHz low-intensity ultrasound on tumors remain unclear. The aim of the present study was to explore the effects of 21 kHz ultrasound with microbubbles on the regulation of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and apoptosis in subcutaneous prostate tumors in nude mice. The study included three parts, each with 20 tumor-bearing nude mice. Twenty nude mice were divided into four groups: control (sham treatment), microbubble ultrasound contrast agent (UCA), low-frequency ultrasound (US) and US+UCA groups. The UCA used was a microbubble contrast agent (SonoVue). The parameter of ultrasound: 21 kHz, an intensity of 26 mW/cm2, 40% duty cycle (on 2 sec, off 3 sec), 3 min, once every other day for 2 weeks. In the first study, all subcutaneous tumors were examined by contrast-enhanced ultrasonography (CEUS) at the initiation and completion of the experiments. Peak intensity (PI), time to peak intensity (TTP) and area under the curve (AUC) on the time intensity curve (TIC) were analyzed. In the second study, the intensity of VEGF and COX-2 protein expression in the vascular endothelium and cytoplasm was evaluated using immunohistochemistry and laser confocal microscopy. In the third study, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay was used for the evaluation of cell apoptosis in tumor tissues. The tumor cells and vasculature were examined by transmission electron microscopy (TEM). Only in the US+UCA group, PI and AUC decreased. The intensity of COX-2 and VEGF in the US+UCA group in immunohistochemical staining and laser confocal microscopy was lower compared to that of the other three groups. More cell apoptosis was found in the US+UCA group compared to the other 3 groups. In the control, UCA and US groups, the tumors had intact vascular endothelium and vessel lumens in TEM. However, lumen occlusion of vessels was observed in the US+UCA group. Twenty-one kHz low-intensity ultrasound with microbubbles may have anti-angiogenic effects on subcutaneous tumors in nude mice.