Using cell culture systems from the Persian Gulf Arabian yellowfin sea bream, Acanthopagrus arabicus, to assess the effects of dexamethasone on gonad and brain aromatase activity and steroid production.

Dexamethasone (DEX) is a synthetic glucocorticoid widely used as pharmaceutical and usually exists in effluents with varying degrees of concentrations. In this study, cultivated Brain, ovary and testis cells from Arabian Sea bream, Acanthopagrus arabicus, were treated by DEX at concentrations of 0, 0.3, 3.0, 30.0 and 300.0 µg/ml for 48 h. The aromatase activity and steroid (17-ß-estradiol (E2), progesterone (P) and testosterone (T)) production by cells were measured at 12, 24 and 48 h of the experiment. The results showed that the sensitivity of cultivated ovarian, testicular and brain cells to DEX increased dose dependently. DEX was potent inhibitor of aromatase activity at specially 30.0 and 300.0 µg/ml in the cultivated ovarian and testicular cells at different sampling time. On the other hand, DEX was found to stimulate the aromatase activity of fish brain. DEX also decreased E2, P and T production by cultivated ovarian and testicular cells during the experiment. While, DEX caused an increase in the production of E2 and P by brain cells, which seems logical considering the stimulating effect of this drug on brain aromatase activity. In conclusion, results highlight that DEX is able to change the activity of aromatase, and disrupt the biosynthesis of estrogens and thus affect reproduction in fish.

Integrative assessment of urban dust polycyclic aromatic hydrocarbons using ground and satellite data in Iran.

Recently, for quick urbanization and industrialization, pollutants, especially urban dust, have posed many threats to the human environment. Polycyclic aromatic hydrocarbons (PAHs) are regarded as the main dangerous pollutants that are widespread, persistent, and carcinogenic. The present work aimed to investigate the contamination and sources of PAHs, as well as to assess the risk of cancer for 16 priority PAHs, in urban dust samples in Ahvaz, Isfahan, and Shiraz cities in Iran. We measured PAH concentrations by gas chromatography-mass spectrometry (GC-MS). The average concentrations of the 16 PAHs in Ahvaz, Isfahan, and Shiraz were 6215.11, 7611.03, and 7810.37 µg kg-1, respectively. The domination of low-molecular-weight (LMW) PAHs was observed in Ahvaz, while maximum contribution was observed for high-molecular-weight (HMW) PAHs in Esfahan and Shiraz. For PAHs' source identification, diagnostic ratio, correlation analysis, clustering, and positive matrix factorization (PMF) model were used. PAHs had a combustion (coal and wood, oil, fossil fuels) and gasoline/diesel engine emissions in all cities. Comparative studies suggest that the PAH compounds' level is higher in the research area than in other countries, except for China and India. Also, the pollution of urban dust PAHs has increased over time compared to previous studies in the same cities. The cancer risk from exposure to dust contaminated with PAHs was assessed using the Incremental Lifetime Cancer Risk (ILCR) model. According to the findings, a high risk of exposure to cancer was observed in Ahvaz, Isfahan, and Shiraz. However, compared to adults, children are at higher risk of cancer in their daily lives via dermal contact and unconscious ingestion. Based on the ILCR values, the risk of cancer is in the order of Shiraz > Isfahan > Ahvaz. To assess air pollutants and their effects on urban dust, TROPOMI onboard the Sentinel-5P data were used in the studied cities during 2018-2021. The results show that Ahvaz has different high levels of CO compared to the other 2 cities. Also, Isfahan has different high levels of NO2 compared to the other 2 cities, but Shiraz has different low levels of O3. According to satellite time series data, the trend of the Aerosol Absorbing Index (AAI) has been increasing, while there was a decreasing trend in AAI from the beginning of the COVID-19 pandemic until 12 months later. Therefore, the natural and anthropogenic sources of urban dust PAHs have been increasing in all studied cities. Our findings show that PAH compounds in urban dust pose a significant threat to human health. Therefore, strategic management and planning are vital in reducing urban dust pollution.

Inhibitory effects of fluoxetine on the secretion of inflammatory mediators and JAK/STAT3 and JNK/TLR4 gene expression.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most common class of medicines used for the treatment of major depression. Recent studies have reported an association between depression and inflammation and suggested the significant effects of SSRIs on inflammatory processes. METHODS: The current study aimed to evaluate the effects of fluoxetine, an SSRI, on the level of inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the rat serum and RAW264.7 mouse macrophage cell line, using ELISA sandwich assays. Also, the expression of inflammatory genes, including JAK/STAT3 and TLR4/JNK, was examined in macrophages, using real-time quantitative reverse transcription PCR to determine the potential mechanism of fluoxetine in inflammation. The rats received fluoxetine (10, 20, and 40 mg/kg) 30 min before lipopolysaccharide (LPS) treatment for 90 min. The cells received different doses of fluoxetine (5, 10, and 20 µg/mL) before stimulation with LPS for 24 or 48 h. RESULTS: The serum concentrations of IL-1ß, IL-6, and TNF-α were reduced in rats and cells treated with fluoxetine. Following fluoxetine administration, the expression of JAK/STAT3 and TLR4/JNK genes was significantly decreased in the RAW264.7 cells treated with LPS for 24 h. However, after 48 h of treatment with LPS, fluoxetine failed to diminish the elevated expression of JAK and JNK genes, while it significantly decreased the expression of STAT3 and TLR4 genes. CONCLUSION: The findings revealed that fluoxetine has anti-inflammatory properties, mainly due to the reduction of inflammatory cytokines and inhibition of JAK/STAT3 and TLR4/JNK gene expression in macrophages.

Temporal and spatial pattern of dust storms, their polycyclic aromatic hydrocarbons, and human health risk assessment in the dustiest region of the world.

This study evaluated the concentration and health risks of polycyclic aromatic hydrocarbons (PAHs) in Abadan City under 4 different climatic conditions: normal days, dusty days, dust with northwesterly winds, and dust with southeasterly winds. It also determined the sources of aromatics and discussed the relationship between meteorological parameters and PAH concentrations. The spatiotemporal distribution of dust in the area was determined using the HYSPLIT (hybrid single-particle Lagrangian integrated trajectory) back trajectory model, moderate resolution imaging spectroradiometer (MODIS) images. For this purpose, sampling was performed for 70 days using an Omni device. The concentrations of 16 PAHs (USEPA) ranged from 46.22 to 90.96 ng/m3. The highest concentration of high molecular weight (HMW) PAHs was 4-6 rings, of which 4 rings were predominant in all samples. PAH sources were identified using diagnostic ratios and principal component analysis (PCA), and it was shown that PAHs mainly originate from a mixture of sources, including vehicular emissions, petrol emissions, and traffic. Wind speed was negatively correlated with dust, except on dusty days. This result indicates a decrease in PAH concentrations when wind speed increases. On the other hand, the dust correlation with PAH was positive on normal days, but a negative correlation was observed on dusty days. This result was due to the lower concentration of PAHs from natural resources (such as dust source areas) vs. human resources (such as traffic and industry). PAH health risk assessment in Abadan City showed that the risk of carcinogenesis was higher on normal days and through skin contact. The probability of incremental lifetime cancer risk (ILCR) in all sampling conditions was potential in terms of carcinogenic risk (10-4-10-6). As a critical risk factor, relevant authorities should prevent, control, and reduce it.

The protective effect of herniarin on genotoxicity and apoptosis induced by cisplatin in bone marrow cells of rats.

Herniarin is a member of simple coumarins, which are a group of common secondary metabolites in plants. The aim of the present study was to investigate the effects of herniarin on genotoxicity and apoptosis induced by cisplatin in rat bone marrow cells. The experimental rats were treated with four different doses of herniarin (50, 100, 200, and 400 mg/kg.) for seven consecutive days. The cisplatin (5 mg/kg, i.p.) was injected into mice 1 h after the last oral herniarin administration on the seventh day. The protective effects of herniarin were investigated by hematological test, flow cytometry, micronucleus assay, and reactive oxygen species (ROS) level analysis. Herniarin caused a marked reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after exposure to cisplatin at doses of 200 and 400 mg/kg. Furthermore, herniarin significantly increased the levels of both red and white blood cells in peripheral blood. Treatment of rats with herniarin before cisplatin, significantly decreased the percentage of apoptotic and necrotic cells and the ROS level in bone marrow cells. This study indicated that herniarin can be introduced as a new chemoprotective agent against cisplatin-induced genotoxicity in the future.

Role of the mesenchymal stem cells derived from adipose tissue in changing the rate of breast cancer cell proliferation and autophagy, in vitro and in vivo.

OBJECTIVES: Autophagy is an intracellular degradation system of damaged proteins and organelles; however, the role of autophagy in the progression of cancer remains unclear. In recent years, mesenchymal stem cell (MSC)-based approaches have attracted considerable attention for anti-cancer therapy. The present study aimed to examine the interaction of MSCs with the breast cancer cells under autophagy-induced conditions. MATERIALS AND METHODS: In this study, MSCs isolated from human adipose tissue were co-cultured with MDA-MB 231, a breast cancer cell line, and the autophagy process was induced by tunicamycin treatment. The cell viability was monitored by the MTT assay, and the cells were recovered at different time intervals (24 or 48 hours) to determine autophagy markers such as Beclin, mTOR and the ratio of LC3II/I expression. Additionally, the animal study was conducted using a mouse model of breast cancer treated with isogenic adipose-derived MSCs, and the expression of Beclin and Ki67 was determined using immunohistochemistry in breast tumor tissue. RESULTS: In cancer cells co-cultured with MSCs, the cell proliferation was increased, the Beclin expression and the LC3II/I protein ratio were decreased, and the mTOR expression was increased in MDA-MB 231 upon co-cultured with MSCs. Direct injection of MSCs to a mouse model of breast cancer showed an increase in tumor volume, an increase in the accumulation of Ki67 and a decrease in the Beclin expression in tumor tissues. CONCLUSION: The data may suggest that suppressed autophagy in breast cancer cells is probably a mechanism by which MSCs can induce cancer cell proliferation.

Selective induced apoptosis and cell cycle arrest in MCF7 and LNCap cell lines by skin mucus from round goby (Neogobius melanostomus) and common carp (Cyprinus carpio) through P53 expression.

The skin mucus in lower vertebrates such as fish with strong innate immune system has many unique and valuable bioactive compounds that can be used for inducing apoptosis in cancer cells. This study was looking for the cytotoxic potential of mucus from the two fish species, including round goby (Neogobius melanostomus) and common carp (Cyprinus carpio), and inducing apoptosis in MCF7 and LNCaP cancer cell lines via influencing P53 gene expression and cell cycle arrest. Results showed that the both mucus types have cytotoxic effects on the both cancer cell lines whereas they have no severe effect on normal primary fibroblast cells. In addition, round goby mucus and common carp mucus selectively induced apoptosis in the LNCaP and MCF7 cells, respectively, through up-regulating P53 gene and arresting cell cycle at the G1 phase. Taken together, this study suggested that the both mucus types can selectively influence P53 pathway and induce apoptosis in especial cancer cells. The skin mucus derived from round Goby and common Carp can be a promising candidate for investigation about apoptosis and molecular targeting therapy in cancer.

Evaluation of Antileishmanial Activity Employing Conventional and Solid Lipid Nanoparticles of Amphotericin B on Leishmania major In Vitro and In Vivo.

BACKGROUND: Obligate intracellular parasites of Leishmania genus belong to the family Trypanosomatidae and more than twenty species cause this neglected vector-borne infection throughout the globe. OBJECTIVE: The current study was aimed to assess the antileishmanial activity of Amphotericin B (AmB) and AmB formulated into solid lipid nanoparticles (SLNs) in vitro and in vivo. MATERIALS AND METHODS: In the present research, microemulsification and high shear homogenization methods were used to prepare SLNs. Leishmania major (L. major) promastigotes were cultured in RPMI 1640 and incubated for three time points of 24, 48 and 72 h at 25±1°C. Then, the MTT colorimetric assay was employed for obtaining 50% inhibitory concentration (IC50). Finally, the efficacy of AmB and AmB-SLN was evaluated for the treatment of experimental cutaneous leishmaniasis (CL) in BALB/c mice. RESULTS: The average diameter sizes of prepared AmB-SLN were <180 nm and monodisperse preparations with polydispersity index 0.21±0.29. The antileishmanial activity of AmB and AmBSLN revealed a dose and time-dependent manner in vitro. The IC50 values of AmB (38.18±1.33, 25.06±2.00, and 13.87±0.61 µg/ml) and AmB-SLN (0.40±0.02, 0.26±0.02, and 0.14±0.01 µg/ml) were estimated after 24, 48 and 72 hours, respectively. In all BALB/c treatment groups, the diameter of lesions was significantly smaller than the control group. CONCLUSION: AmB-SLN was significantly more potent than AmB in vitro and in vivo. The discovery of new effective drugs based on nanocarriers, such as SLN, is practical and opens a new window for the treatment of CL.

Valsartan attenuates bleomycin-induced pulmonary fibrosis by inhibition of NF-κB expression and regulation of Th1/Th2 cytokines.

OBJECTIVE: Pulmonary fibrosis (PF) is a chronic respiratory system disease. The role of inflammation and angiotensin in the development and progression of PF has previously been demonstrated. Alternation in antifibrotic/profibrotic mediators and NF-κB activation have important roles in PF development. NF-κB, a nuclear factor, induces the transcription of inflammatory and pro-inflammatory cytokines. The aim of this study was to evaluate the effect of valsartan as an angiotensin receptor blocker on IL-4, INF-γ, and NF-κB expression in the treatment of PF. MATERIALS AND METHODS: Rats were divided into five groups: groups I (bleomycin) and II (control) received a single injection of bleomycin (7.5 IU/kg) or vehicle, respectively. Groups III-V received valsartan (20, 40, and 80 mg/kg, respectively) orally a week before and for 3 weeks after the bleomycin injection. Serum levels of IL-4 and INF- γ were then measured. Relative NF-κB expression was investigated by real-time PCR. RESULTS: Histopathological examination showed the anti-inflammation effect of valsartan. Bleomycin significantly increased IL-4 serum level and decreased that of INF-γ in the serum. Valsartan could restore their levels to normal. Valsartan raised the decreased ratio of INF-γ/IL-4. Exposure to bleomycin elevated NF-κB expression; and valsartan decreased the increased gene expression. DISCUSSION: Valsartan as an angiotensin receptor antagonist presumably by blocking angiotensin receptor causes to ameliorated PF, which was at least partly due to antifibrotic/profibrotic cytokine regulation and reduced NF-κB expression. CONCLUSIONS: Valsartan showed a significant protective effect against bleomycin-induced PF.

The role of calcium channel blockers in wound healing.

Wound healing is a natural response to restore the injured tissue to normal. Wound healing is also complicated process involving different cellular, molecular and biochemical mechanisms and various types of cytokines and growth factors. Calcium channel blockers belong to cardiovascular medicine and administrated to treatment of hypertension, angina and cardiac arrhythmia because of vasodilatory effect. Calcium channel blockers is divided to dihydropyridine and non-dihydropyrine. The potential of both dihydropyridine and non-dihydropyrine calcium channel blockers in wound healing have been reported in different animal models and in vitro previously. Amlodipine, verapamil, diltiazem, nifedipine, and azelnidipine are calcium channel blockers that indicated wound healing property. The various mechanisms that involve in wound healing effect of calcium channel blockers are discussed in this article.

Effects of herbal extracts and compounds and pharmacological agents on pulmonary fibrosis in animal models: a review.

Pulmonary fibrosis, a chronic inflammatory disease that occurs mainly in older adults, is a serious health threat with few effective treatment options. The etiological aspects of pulmonary fibrosis remain unknown, though some factors such as cigarette smoking, viral infections, surfactant protein polymorphisms, and chronic or high doses use of certain drugs are considered to be risk factors for the progression of pulmonary fibrosis. No standard treatments have been introduced in clinic yet. Although glucocorticoids and antioxidant drugs have been administered, the severe and broad-spectrum adverse effects of glucocorticoids limit their use. Efforts to identify novel therapeutic agents with improved safety profiles are therefore ongoing. In this review, the authors have described the effects of herbal extracts and compounds and certain pharmacological agents on pulmonary fibrosis in animal models. These effects indicate that herbs are a promising source of compounds that can play pivotal roles in the treatment of lung fibrosis.

Wound healing potential of topical amlodipine in full thickness wound of rabbit.

BACKGROUND: Wound healing is a complicated and integrated process. Researches have indicated the wound healing effects of calcium channel blockers in animal models in recent years. OBJECTIVES: The aim of this study was to evaluate the wound-healing activity of amlodipine as a calcium channel blocker and combination of amlodipine with phenytoin on excisional cutaneous wound models in rabbit. MATERIALS AND METHODS: Animals were divided into 5 groups (n = 5). The control group was treated topically with eucerin. The untreated control group received no healing agent. The reference standard group was treated with phenytoin1%. A treatment group was treated with amlodipine 1%. The last group was treated with combination of amlodipine1% and phenytoin 1%. RESULTS: Results indicated significant difference between days needed for complete healing in both of the treatment groups. Wound closure was completed on 13th day and 9th day in amlodipine and combination groups respectively. CONCLUSIONS: In conclusion, calcium channel blockers can be used to enhance wound healing, especially if this treatment becomes with phenytoin. Further studies are needed to find out the mechanism of this healing effect.