RESUMEN

Testicular injury and affected spermatogenesis are major complications of methotrexate (MTX) use. Oxidative stress is one contributing process leading to inflammation and apoptosis induction. Pirfenidone (PFD) is a well-known anti-fibrotic drug prescribed for interstitial lung fibrosis, in addition to anti-inflammatory, antioxidative, and antiapoptotic capabilities. The study aimed to explore the potential protection afforded by PFD in a rat model of MTX-induced testiculopathy. The experimental design included four groups, each containing seven adult Wistar rats: control, PFD (500 mg/kg/day, orally)-, MTX (0.5 mg/kg, intraperitoneal, twice weekly)-, and PFD/MTX-treated groups. Treatment continued for 4 weeks. Blood and testicular samples were harvested for biochemical, histological, immunohistochemical, and polymerase chain reaction (PCR) analyses. Also, the testicular damage and spermatogenic activity were graded by the testicular injury and Johnsen scoring system, respectively. PFD positively affected the serum testosterone (TST) level, reduced the testicular inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß)], reduced the testicular oxidative burden, increased superoxide dismutase (SOD), and protected the testicular histological structure. In addition, antifibrotic effects, anti-caspase-3, and PCNA enhancement activity were recorded. PFD exhibited a protective potential and mitigated the MTX-induced testiculopathy via suppression of testicular oxidative stress, inflammation, fibrosis, and apoptosis and retaining the testicular proliferative efficacy as confirmed by histological, immunohistochemical, and biochemical methods.

RESUMEN

Staphylococcus aureus poses a significant threat in both community and hospital settings due to its infective and pathogenic nature combined with its ability to resist the action of chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) poses a critical challenge. Metal-chelating thiosemicarbazones (TSCs) have shown promise in combating MRSA and while previous studies hinted at the antimicrobial potential of TSCs, their mechanisms of action against MRSA are still under investigation. We screened a chemical library for anti-staphylococcal compounds and identified a potent molecule named R91 that contained the NNSN structural motif found within TSCs. We identified that R91 and several structural analogs exhibited antimicrobial activity against numerous S. aureus isolates as well as other Gram-positive bacteria. RNAseq analysis revealed that R91 induces copper and oxidative stress responses. Checkerboard assays demonstrated synergy of R91 with copper, nickel, and zinc. Mutation of the SrrAB two-component regulatory system sensitizes S. aureus to R91 killing, further linking the oxidative stress response to R91 resistance. Moreover, R91 was found to induce hydrogen peroxide production, which contributed to its antimicrobial activity. Remarkably, no mutants with elevated R91 resistance were identified, despite extensive attempts. We further demonstrate that R91 can be used to effectively treat an intracellular reservoir of S. aureus in cell culture and can reduce bacterial burdens in a murine skin infection model. Combined, these data position R91 as a potent TSC effective against MRSA and other Gram-positive bacteria, with implications for future therapeutic development.

RESUMEN

Arsenic (As) is globally detected in drinking water and food products at levels repeatedly surpassing regulatory thresholds. Several neurological and mental health risks linked to arsenic exposure are proposed; however, the nature of these effects and their association with the chemical forms of arsenic are not fully understood. Gaining a clear understanding of the etiologies and characteristics of these effects is crucial, particularly in association with developmental exposures where the nervous system is most vulnerable. In this study, we investigated the effects of early developmental exposure (6- to 120-h postfertilization [hpf]) of larval zebrafish to environmentally relevant concentrations of arsenic species-trivalent/pentavalent, inorganic/organic forms-on developmental, behavioral, and molecular endpoints to determine their effect on stress response and their potential association with stress-related disorders. At 120 hpf, the developing larvae were assessed for a battery of endpoints including survival, developmental malformities, background activity, and behavioral responses to acute visual and acoustic stimuli. Pooled larval samples were analyzed for alterations in the transcript levels of genes associated with developmental neurotoxicity and stress-related disorders. Developmental exposures at target concentrations did not significantly alter survival, overall development, or background activity, and had minor effects on developmental morphology. Sodium arsenate and monomethylarsonic acid exaggerated the behavioral responses of larval zebrafish, whereas sodium arsenite depressed them. Sodium arsenate induced significant effects on molecular biomarkers. This study highlights the effects of developmental exposure to arsenicals on the behavioral stress response, the role chemical formulation plays in exerting toxicological effects, and the possible association with stress-related disorders.

Asunto(s)

Conducta Animal , Larva , Pez Cebra , Animales , Larva/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Compuestos de Sodio/toxicidad , Contaminantes Químicos del Agua/toxicidad , Arsenitos/toxicidad , Estrés Fisiológico/efectos de los fármacos , Arsénico/toxicidad , Arseniatos/toxicidad

RESUMEN

Behavioral assays using early-developing zebrafish (Danio rerio) offer a valuable supplement to the in vitro battery adopted as new approach methodologies (NAMs) for assessing risk of chemical-induced developmental neurotoxicity. However, the behavioral assays primarily adopted rely on visual stimulation to elicit behavioral responses, known as visual motor response (VMR) assays. Ocular deficits resulting from chemical exposures can, therefore, confound the behavioral responses, independent of effects on the nervous system. This highlights the need for complementary assays employing alternative forms of sensory stimulation. In this study, we investigated the efficacy of acoustic stimuli as triggers of behavioral responses in larval zebrafish, determined the most appropriate data acquisition mode, and evaluated the suitability of an acoustic motor response (AMR) assay as means to assess alterations in brain activity and risk of chemical-induced developmental neurotoxicity. We quantified the motor responses of 120 h post-fertilization (hpf) larvae to acoustic stimuli with varying patterns and frequencies, and determined the optimal time intervals for data acquisition. Following this, we examined changes in acoustic and visual motor responses resulting from exposures to pharmacological agents known to impact brain activity (pentylenetetrazole (PTZ) and tricaine-s (MS-222)). Additionally, we examined the AMR and VMR of larvae following exposure to two environmental contaminants associated with developmental neurotoxicity: arsenic (As) and cadmium (Cd). Our findings indicate that exposure to a 100 Hz sound frequency in 100 ms pulses elicits the strongest behavioral response among the acoustic stimuli tested and data acquisition in 2 s time intervals is suitable for response assessment. Exposure to PTZ exaggerated and depressed both AMR and VMR in a concentration-dependent manner, while exposure to MS-222 only depressed them. Similarly, exposure to As and Cd induced respective hyper- and hypo-activation of both motor responses. This study highlights the efficiency of the proposed zebrafish-based AMR assay in demonstrating risk of chemical-induced developmental neurotoxicity and its suitability as a complement to the widely adopted VMR assay.

Asunto(s)

Estimulación Acústica , Actividad Motora , Pez Cebra , Animales , Estimulación Acústica/métodos , Actividad Motora/efectos de los fármacos , Síndromes de Neurotoxicidad/fisiopatología , Síndromes de Neurotoxicidad/etiología , Larva/efectos de los fármacos , Aminobenzoatos/toxicidad , Estimulación Luminosa/métodos

RESUMEN

Reproductive aging is associated with altered stress response and many other menopausal symptoms. Little is known about the adrenal expression of the anti-aging protein Klotho or how it is modulated by estrogen in ovariectomized stressed rats. Fifty-six Wistar female rats were assigned into seven equal groups. Sham-operated (Sham), sham stressed (Sham/STS), ovariectomized (OVR), ovariectomized stressed (OVR/STS), ovariectomized stressed rosiglitazone-treated (OVR/STS/R), ovariectomized stressed estrogen-treated (OVR/STS/E), and ovariectomized stressed estrogen/GW9662 co-treated (OVR/STS/E/GW) groups. All stressed rats were subjected daily to a one-hour restraint stress test for 19 days. At the end of the experiment, blood was collected for serum corticosterone (CORT) analysis. Adrenal tissues were obtained and prepared for polymerase chain reaction (PCR) assay, hematoxylin and eosin (H&E), immunohistochemistry-based identification of Klotho and PPAR-γ, and Oil Red O (ORO) staining. The rise in serum CORT was negligible in the OVR/STS group, in contrast to the Sham/STS group. The limited CORT response in the former group was restored by estrogen and rosiglitazone and blocked by estrogen/GW9226 co-administration. ORO-staining revealed a more evident reduction in the adrenal fat in the OVR/STS group, which was reversed by estrogen and counteracted by GW. Also, there was a comparable expression pattern of Klotho and PPAR-γ in the adrenals. The adrenal Klotho decreased in the OVR/STS group, but was reversed by estrogen treatment. GW9226/estrogen co-treatment interfered with the regulatory effect of estrogen on Klotho. The study suggested modulation of the adrenal Kotho expression by estrogen, in the ovariectomized rats subjected to a restraint stress test. This estrogen-provided adrenal protection might be mediated by PPAR-γ activation.

Asunto(s)

Corteza Suprarrenal , Estrógenos , Glucuronidasa , Proteínas Klotho , Ovariectomía , PPAR gamma , Ratas Wistar , Animales , Femenino , Glucuronidasa/metabolismo , Glucuronidasa/genética , Corteza Suprarrenal/metabolismo , Corteza Suprarrenal/efectos de los fármacos , PPAR gamma/metabolismo , PPAR gamma/genética , Ratas , Restricción Física , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Corticosterona/sangre , Estrés Psicológico/metabolismo , Estrés Fisiológico , Rosiglitazona/farmacología , Modelos Animales de Enfermedad , Envejecimiento/metabolismo , Modelos Animales

RESUMEN

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals known for their widespread use and persistence in the environment. Laboratory and epidemiological studies investigating these compounds have signaled their neurotoxic and endocrine-disrupting propensities, prompting further research into their effects on behavioral stress responses and their potential role as risk factors for stress-related disorders such as anxiety and depression. This study elucidates the ramifications of early developmental exposures to individual and combined PFAS on the development and behavioral stress responses of larval zebrafish (Danio rerio), an established model in toxicological research. Wild-type zebrafish embryos were enzymatically dechorionated and exposed to PFOS, PFOA, PFHxS, and PFHxA between 6 and 120 h post-fertilization (hpf). We targeted environmentally relevant concentrations stemming from the USEPA 2016 Hazard Advisory Limit (HAL, 0.07 µg/L) and folds higher (0.35, 0.7, 1.75, and 3.5 µg/L). Evaluations at 120 hpf encompassed mortality, overall development, developmental defects, and larval activity both at baseline stress levels and following exposure to acute stressors (acoustic and visual). Larval exposure to PFOA, PFOS, or PFHxS (0.07 µg/L or higher) elicited significant increases in mortality rates, which capped at 23.1%. Exposure to individual chemicals resulted in limited effects on overall development but increased the prevalence of developmental defects in the body axis, swim bladder, pigmentation, and eyes, as well as the prevalence of yolk sac and pericardial edemas. Larval activity at baseline stress levels and following exposure to acute stimuli was significantly altered. Combined exposure to all four chemicals intensified the breadth of developmental and behavioral alterations, suggesting possible additive or synergistic effects. Our findings shed light on the developmental and neurobehavioral disturbances associated with developmental exposure to PFAS at environmentally relevant concentrations, the added risks of combined exposures to these chemicals, and their possible role as environmental risk factors for stress-related disorders.

Asunto(s)

Conducta Animal , Fluorocarburos , Larva , Contaminantes Químicos del Agua , Pez Cebra , Animales , Fluorocarburos/toxicidad , Larva/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Conducta Animal/efectos de los fármacos , Estrés Fisiológico , Embrión no Mamífero/efectos de los fármacos

RESUMEN

BACKGROUND AND OBJECTIVES: Despite much research about lupus nephritis, none of the urinary biomarkers has been proven to be truly reflecting lupus nephritis activity, response to treatment, or prognosis. We aimed to study urinary biomarkers in lupus nephritis and test their relation to kidney damage. PATIENTS AND METHODS: Forty patients with systemic lupus erythematosus (SLE) were divided into two graoups: (1) lupus nephritis group with biopsy-proven proliferative lupus nephritis (classes III and IV) and who did not receive immunosuppressive drugs within the preceding 3 months except for glucocorticoids and (2) lupus non-nephritis group with SLE patients without any renal manifestation. We assessed disease activity by the SLE disease activity index. uNGAL, uKim-1, uNGAL to urinary creatinine excretion (mg/dl), and uKim-1 to urinary creatinine excretion were measured in random spot urine samples at the time of renal biopsy and 6 months after the induction therapy. RESULTS: The LN group before treatment showed higher levels of uNGAL and uKIM-1 (P-value < 0.001). ROC analysis showed that uNGAL at level of > 59 has a 95 % sensitivity, a 100 % specificity, and an AUC = 0.996 in the ability to diagnose LN. While the uKIM-1 ROC showed that at level of > 1.6, it has an 85 % sensitivity, an 80 % specificity, and an AUC = 0.919. uNGAL and uKIM levels were significantly lower after treatment (P-value < 0.001). No significant correlations were found between urinary markers before and after treatment with other clinical, inflammatory, and serological markers of lupus nephritis. CONCLUSION: uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio can be used as a predictor and a marker of disease activity for lupus nephritis. Key Points • Renal biopsy is the current standard for diagnosis of lupus nephritis and none of the urinary biomarkers has been fully concluded to have a diagnostic power to reflect the activity or the response to treatment. • However, based on the finding of the current study, uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio showed significant diagnostic performance and were powerful indices of renal involvement in systemic lupus patients and as markers of disease activity.

Asunto(s)

Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Biomarcadores , Creatinina/orina , Riñón/patología , Lipocalina 2/orina , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/patología

RESUMEN

Bisphenol-A (BPA) is a synthetic chemical compound broadly used in the plastic and epoxy resin industries with a considerable potential for food contamination. Literary reports have suggested that the altered renin-angiotensin system (RAS) is a mechanism for lung injury and inflammation caused by variable agents. The current study sought to investigate the contribution of RAS to BPA-induced lung damage. Moreover, the study assessed whether angiotensin II and/or bradykinin pathways were involved. For this aim, the angiotensin-converting enzyme (ACE) inhibitor captopril (Cap), either alone or combined with bradykinin receptor antagonist icatibant (Icat), was attempted versus the angiotensin receptor blocker losartan (Los). An eight-week study was conducted on forty Wistar male albino rats randomly divided into five equal groups: control, BPA, BPA/Cap, BPA/Los, and BPA/Cap/Icat groups. Captopril (100 mg/mL) and losartan (200 mg/mL) were given orally in drinking water, but icatibant (Icat) was injected subcutaneously (250 µg/kg) during the last two weeks of captopril treatment. Biochemical analysis of bronchoalveolar lavage fluid (BALF) and lung tissues, polymerase chain reaction (PCR) assay for ACE, ACE2, and caspase-3 genes expression, and histological and immunohistochemical studies were carried out to evaluate BPA-mediated pulmonary inflammation/apoptosis. BPA impaired the histological structure of the lungs, increased ACE, ACE2, and caspase-3 expressions at both gene/protein levels, and increased BALF inflammatory cytokines and lung oxidative markers. Inhibiting the ACE activity by captopril maintained the histological lung injury score, restored inflammation and the ACE2/ACE balance, and decreased apoptosis. Further improvement was obtained by the angiotensin II receptor (ATR1) blocker losartan. Icatibant (bradykinin B2 receptor blocker) didn't counteract the observed captopril effects. It was strongly suggested that RAS contributed to BPA-induced lung damage via alteration of ACE2 and ACE expression mediating angiotensin II generation rather than bradykinin.

RESUMEN

Key Clinical Message: Poncet's disease is an acute onset reactive polyarthritis associated with tuberculosis infection. Although uncommon, the diagnosis should be considered among patients presenting with symmetrical polyarthritis in tuberculosis-endemic regions. Abstract: This is a case report of Poncet's disease presenting as bilateral knee and wrist pain associated with swelling. Joint x-rays and immunological assays were normal. A chest x-ray and Gene-Xpert diagnosed tuberculosis. A complete resolution of symptoms was attained following the completion of antituberculous therapy regimen.

RESUMEN

The effect of bisphenol-A (BPA) on Klotho protein (aging-suppressing protein) expression in different body organs has not been sufficiently addressed by literature studies. The study investigated the impact of BPA on Klotho expression in multiple organs including the liver, kidney, and pancreas and suggested the involved molecular pathways. Twenty-seven male Wistar albino rats were divided into 3 equal groups: control, low-dose BPA (4.5 µg/L), and high-dose BPA (8 µg/L) groups in drinking water for 45 consecutive days. Liver, kidney, and pancreatic specimens were prepared for a gene study of Klotho, HSP60, mTOR, and ULK1 mRNA expressions. Also, the tissue specimens were measured for malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels. Paraffin-embedded sections were also prepared and subjected to Hematoxylin and Eosin (H&E) staining and immunohistochemical detection of Klotho and HSP60. The results revealed an alteration in the MDA, SOD, NO tissue levels, disturbed gene expression profile, and apoptotic changes in the histological findings of the examined organs which were obvious (p < 0.05) in the high-dose group. The anti-aging Klotho gene/protein expression was reduced (p < 0.05) more in the high-dose BPA group than in the low dose. In contrast, HSP60 gene/protein expression was significantly increased (p < 0.05) more in the high dose. It was concluded that BPA exposure contributed to cell stress and markedly reduced Klotho protein expression in liver, kidney, and pancreatic tissues, possibly by modulation of the HSP60-activated mTOR/autophagy signaling.

Asunto(s)

Riñón , Hígado , Masculino , Ratas , Animales , Páncreas , Serina-Treonina Quinasas TOR/genética , Autofagia , Óxido Nítrico

RESUMEN

The incorporation of fermented camel milk with natural additives possesses numerous benefits for the treatment of various pathological and metabolic conditions. The present study investigated the impact of fortification of fermented camel milk with sage or mint leaves powder (1 and 1.5%, respectively) on glucose and insulin levels, lipid profile, and liver and kidney functions in alloxan-induced diabetic rats. The gross chemical composition of sage and peppermint leaves powder was studied. The chemical composition of sage and mint extracts was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS) of sage and mint extracts. Furthermore, a total of forty-two adult normal male albino rats were included in this study, whereas one group was kept as the healthy control group (n = 6 rats) and diabetes was induced in the remaining animals (n = 36 rats) using alloxan injection (150 mg/kg of body weight). Among diabetic rats groups, a control group (n = 6 rats) was kept as the diabetic control group whereas the other 5 groups (6 rats per group) of diabetic rats were fed fermented camel milk (FCM) or fermented camel milk fortified with 1 and 1.5% of sage or mint leaves powder. Interestingly, the oral administration of fermented camel milk fortified with sage or mint leaves powder, at both concentrations, caused a significant decrease in blood glucose level and lipid profile, and an increase in insulin level compared to the diabetic control and FCM groups. Among others, the best results were observed in the group of animals that received fermented camel milk fortified with 1.5% sage powder. In addition, the results revealed that the fermented camel milk fortified with sage or mint leaves powder improved the liver and kidney functions of diabetic rats. Our study concluded that the use of sage and mint leaves powder (at a ratio of 1.5%) with fermented camel milk produces functional food products with anti-diabetic activity.

Asunto(s)

Diabetes Mellitus Experimental , Insulinas , Mentha , Salvia officinalis , Ratas , Masculino , Animales , Leche/química , Mentha piperita , Salvia officinalis/química , Camelus , Polvos/análisis , Diabetes Mellitus Experimental/tratamiento farmacológico , Aloxano , Mentha/química , Lípidos/análisis , Hojas de la Planta , Extractos Vegetales/farmacología , Extractos Vegetales/análisis

RESUMEN

Although the classic form of asthma is characterized by chronic pneumonitis with eosinophil infiltration and steroid responsivity, asthma has multifactorial pathogenesis and various clinical phenotypes. Previous studies strongly suggested that chemical exposure could influence the severity and course of asthma and reduce its steroid responsiveness. Cypermethrin (CYP), a common pesticide used in agriculture, was investigated for the possible aggravation of the ovalbumin (OVA)-induced allergic pneumonitis and the possible induction of steroid resistance in rats. Additionally, it was investigated whether pirfenidone (PFD) could substitute dexamethasone, as an alternative treatment option, for the induced steroid resistance. Fifty-six male Wistar albino rats were randomly divided into seven groups: control, PFD alone, allergic pneumonitis, CYP alone, allergic pneumonitis/CYP-exposed, allergic pneumonitis/CYP/dexamethasone (Dex), and allergic pneumonitis/CYP/PFD-treated groups. Allergic pneumonitis was induced by three intraperitoneal OVA injections administered once a week, followed by an intranasal OVA instillation challenge. CYP (25 mg/kg/d), Dex (1 mg/kg/d), and PFD (100 mg/kg/d) were administered orally from day 15 to the end of the experiment. Bronchoalveolar lavage fluid (BALF) was analyzed for cytokine levels. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS)-stained lung sections were prepared. Immunohistochemical identification of p38 MAPK and lung macrophages was performed. The inflammatory/oxidative status of the lung and PCR-quantification of the STAT6, p38 MAPK, MUC5AC, and IL-13 genes were carried out. The allergic pneumonitis-only group showed eosinophil-mediated inflammation (p < 0.05). Further CYP exposure aggravated lung inflammation and showed steroid-resistant changes, p38 activation, neutrophil-mediated, M1 macrophage-related inflammation (p < 0.05). All changes were reversed (p < 0.05) by PFD, meanwhile not by dexamethasone treatment. Pirfenidone could replace dexamethasone treatment in the current rat model of CYP-induced severe steroid-resistant asthma via inhibiting the M1 macrophage differentiation through modulation of the STAT6/p38 MAPK pathway.

Asunto(s)

Alveolitis Alérgica Extrínseca , Asma , Neumonía , Animales , Ratas , Masculino , Ovalbúmina/efectos adversos , Ratas Wistar , Asma/inducido químicamente , Asma/tratamiento farmacológico , Asma/genética , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Inflamación , Macrófagos/metabolismo , Dexametasona/efectos adversos , Fenotipo , Proteínas Quinasas p38 Activadas por Mitógenos/genética

RESUMEN

Monitoring of water retention behavior in soils is an essential process to schedule irrigation. To this end, soil moisture tensiometers usually equipped with mechanical manometers provide an easy and cost-effective monitoring of tension in unsaturated soils. Yet, periodic manual monitoring of many devices is a tedious task hindering the full exploitation of soil moisture tensiometers. This research develops and lab validates a low cost IoT soil moisture tensiometer. The IoT-prototype is capable of measuring tension up to -80 Kpa with R2 = 0.99 as compared to the same tensiometer equipped with a mechanical manometer. It uses an ESP32 MCU, BMP180 barometric sensor and an SD card module to upload the measured points to a cloud service platform and establishes an online soil water potential curve. Moreover, it stores the reading on a micro-SD card as txt file. Being relatively cheap (76 USD) the prototype allows for more extensive measurements and, thus, for several potential applications such as soil water matric potential mapping, precision irrigation, and smart irrigation scheduling. In terms of energy, the prototype is totally autonomous, using a 2400 mAh Li-ion battery and a solar panel for charging, knowing that it uses deep sleep feature and sends three data points to the cloud each 6 h.

RESUMEN

The use of 3-dimensional (3-D) printing is gaining popularity in life sciences and driving innovation in fields including aquatic sperm cryopreservation. Yet, little is known about the effects leachates from these objects may have on biological systems. In this study, we investigated if exposure to leachates from 3-D printed objects fabricated from different photo-curable resins could affect sperm quality in two model fish species, zebrafish (Danio rerio) and goldfish (Carassius auratus). Leachates were collected following contact periods of 10 min and 22 h with objects manufactured using a mask LCD resin printer and three different commercially available resins (i.e., standard, eco-friendly, and impact-resistant). Sperm cells were exposed to the leachates for 18 min, and parameters related to sperm motility, cell count, and membrane integrity were evaluated. All experiments were blinded. Leachate originating from contact with impact-resistant resin for 10 min significantly reduced the cell count of zebrafish sperm, while leachate originating from contact with standard resin for 22 h significantly increased the beat cross frequency of goldfish sperm. The changes were not observed across species and no adverse effects were recorded in percent motility, velocity, amplitude of lateral head movement, or membrane integrity of sperm. Our findings demonstrate that exposure to leachates from certain 3-D printed resins can affect sperm quality, while other resins may support sperm quality evaluation. Further investigations are warranted to assess other parameters, effects, and their biological relevance for a variety of aquatic species.

Asunto(s)

Contaminantes Químicos del Agua , Pez Cebra , Animales , Masculino , Motilidad Espermática , Contaminantes Químicos del Agua/toxicidad , Semen , Espermatozoides , Carpa Dorada

RESUMEN

Unfortunately, humanity is exposed to mixed plasticizers such as bisphenol-A (BPA) and dibutyl phthalate (DBP) that are leached from the daily used plastic products. Previous studies have demonstrated their potential in pancreatic beta cell injury and diabetes induction. The study hypothesized that both compounds would affect the pancreatic alpha cells in albino rats when administered at environmentally relevant doses. Heat shock protein 60 (HSP60) and caspase-3 protein expression was also investigated as potential mechanisms. Thirty-six male Wistar albino rats were separated into four equal groups: control, BPA alone, DBP alone, and BPA + DBP combined groups. BPA and DBP were given in drinking water for 45 days in a dose of 4.5 and 0.8 µg/L, respectively. Fasting blood glucose, serum insulin, pancreatic tissue levels of malondialdehyde, and superoxide dismutase were measured. Pancreatic sections were subjected to hematoxylin & eosin (H & E) staining, glucagon, HSP60, and caspase-3 immunohistochemistry. Although all three experimental groups showed diffuse islet cell HSP60 immunoreactivity, rats exposed to BPA alone showed α-cell-only apoptosis, indicated by H & E changes and caspase-3 immunoreactivity, associated with reduced glucagon immunoreaction. However, rats exposed to DBP alone showed no changes in either α or ß-cells. Both combined-exposed animals displayed α and ß apoptotic changes associated with islet atrophy and reduced glucagon expression. In conclusion, the study suggested HSP60/caspase-3 interaction, caspase-3 activation, and initiation of apoptosis in α-cell only for BPA-alone exposure group, meanwhile DBP alone did not progress to apoptosis. Interestingly, both α/ß cell effect was observed in the mixed group implying synergetic/additive action of both chemicals when combined.

Asunto(s)

Dibutil Ftalato , Células Secretoras de Glucagón , Animales , Ratas , Masculino , Dibutil Ftalato/toxicidad , Caspasa 3/metabolismo , Chaperonina 60 , Glucagón , Ratas Wistar , Compuestos de Bencidrilo/toxicidad

RESUMEN

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of fertile females. It has been reported that stevia leaf extract (SLE) has antidiabetic and antihyperlipidemic properties. Therefore, the current study hypothesized and investigated the role and mechanistic aspects of a natural sweetener; SLE in treating a rat model of letrozole-induced PCOS and to compare it with metformin. Thirty-five female Wistar albino rats were divided into 5 groups: control, PCOS-induced group (letrozole, 1 mg/kg/d, for 21 days), SLE, metformin, and combination-treated groups (300 mg/kg/d, for the next 28 days in SLE and metformin-treated groups). Vaginal smears were done. The levels of glucose, lipid, and hormonal profiles were measured in the serum meanwhile, malonyl dialdehyde (MDA), superoxide dismutase (SOD), and tumour necrosis factor (TNF-α) were measured in the ovary. Ovarian sections were subjected to hematoxylin and eosin, Masson, and immunohistochemical identification of VEGF and TGF-ß followed by morphometric analysis. PCOS rats showed altered hormonal and lipid profiles, in addition to hyperglycemia. Also, the ovarian tissue levels of MDA and TNF-α were elevated, and SOD was decreased. Numerous cystic follicles, decrease/absence of corpora lutea, interstitial fibrosis with positive VEGF and TGF-ß immunoreactivity were evident. SLE improved all altered parameters. SLE showed potential therapeutic merits in letrozole-induced PCOS via anti-inflammatory, antioxidant, anti-fibrotic, and angiogenesis regulating mechanisms. Its effects were almost comparable to metformin, and the combination of both has no further synergistic effect.

RESUMEN

When managing coronavirus disease 2019 (COVID-19) patients, radiological imaging complements clinical evaluation and laboratory parameters. We aimed to assess the sensitivity of chest radiography findings in detecting COVID-19, describe those findings, and assess the association of positive chest radiography findings with clinical and laboratory findings. A multicentre, cross-sectional study was conducted involving all primary health care corporation-registered patients (2485 patients) enrolled over a 1-month period during the peak of the 2020 pandemic wave in Qatar. These patients had reverse transcription-polymerase chain reaction-confirmed COVID-19 and underwent chest radiography within 72 hours of the swab test. A positive result on reverse transcription-polymerase chain reaction was the gold standard for diagnosing COVID-19. The sensitivity of chest radiography was calculated. The airspace opacities were mostly distributed in the peripheral and lower lung zones, and most of the patients had bilateral involvement. Pleural effusion was detected in some cases. The risk of having positive chest X-ray findings increased with age, Southeast Asian nationality, fever, or a history of fever and diarrhoea. Patients with cardiac disease, obesity, hypertension, diabetes, and chronic kidney disease were at a higher risk of having positive chest X-ray findings. There was a statistically significant increase in the mean serum albumin, white blood cell count, neutrophil count, and serum C-reactive protein, hepatic enzymes, and total bilirubin with an increase in the radiographic severity score.

Asunto(s)

COVID-19/diagnóstico , Pulmón/diagnóstico por imagen , Adolescente , Adulto , Factores de Edad , Anciano , Bilirrubina/sangre , Proteína C-Reactiva/análisis , COVID-19/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Fiebre , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Enfermedades no Transmisibles , Pandemias , Derrame Pleural/diagnóstico por imagen , Atención Primaria de Salud , Qatar/epidemiología , Factores Raciales , Estudios Retrospectivos , Sensibilidad y Especificidad , Albúmina Sérica , Rayos X , Adulto Joven

RESUMEN

An increasing number of compounds in our diet and environment are being identified as estrogenic, causing serious and detrimental effects on human, animal, and ecosystem health. Time- and cost-effective biological tools to detect and screen these compounds with potential high-throughput capabilities are in ever-growing demand. We generated a knock-in zebrafish transgenic line with enhanced green fluorescent protein (EGFP) driven by the regulatory region upstream of vitellogenin 1 (vtg1), a well-studied biomarker for estrogenic exposure, using CRISPR/Cas9 technology. Exposure to 17ß-estradiol (E2: 0-625 nM) starting at 4-h post-fertilization in dechorionated embryos resulted in the significant induction of hepatic EGFP with ≥5 nM E2 as early as 3-days post-fertilization. Concentration- and time-dependent increase in the percentage of hepatic EGFP-positive larvae and extent of fluorescence expression, categorized into 3 expression levels, were observed with E2 exposure. A strong correlation between the levels of EGFP mRNA, vtg1 mRNA, and EGFP fluorescence levels were detected. Image analysis of the area and intensity of hepatic EGFP fluorescence resulted in high-fidelity quantitative measures that could be used in automated screening applications. In addition, exposure to bisphenol A (0-30 µM) resulted in quantitative responses showing promise for the use of this transgenic line to assess estrogenic activity of endocrine-disrupting chemicals. These results demonstrate that this novel knock-in zebrafish reporter allows for distinct screening of in vivo estrogenic effects, endpoints of which can be used for laboratory testing of samples for estimation of possible human and environmental risks.

Asunto(s)

Sistemas CRISPR-Cas , Estrógenos/metabolismo , Estrógenos/farmacología , Técnicas de Sustitución del Gen/métodos , Proteínas Fluorescentes Verdes/metabolismo , Animales , Animales Modificados Genéticamente , Compuestos de Bencidrilo/farmacología , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/metabolismo , Disruptores Endocrinos/farmacología , Monitoreo del Ambiente/métodos , Estradiol/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas Fluorescentes Verdes/genética , Larva/metabolismo , Hígado/metabolismo , Datos de Secuencia Molecular , Fenoles/farmacología , ARN Mensajero/metabolismo , Vitelogeninas/genética , Vitelogeninas/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo

RESUMEN

In this study, electrospun cellulose acetate - poly(ethylene oxide) nanofibrous membrane was found to be unique in immobilizing bacterial cells. Here, removal of methylene blue in aqueous media was achieved by using isolated species of bacteria (Bacillus paramycoides) from industrial wastewater and immobilized on cellulose acetate- poly(ethylene oxide) nanofibers using DMSO as a solvent. The decolorization time was varied from 0 to 72 h, different dye concentrations from 20 to 200 mg/L and bacterial cells count was investigated to achieve the maximum MB removal by bacteria-immobilized CA/PEO nanofibrous membrane. The effective dye decolorization was achieved within 48 h and MB removal % was around 93%. Furthermore, reusability of the bacteria-immobilized CA/PEO nanofibrous membrane was tested. It was found that after the 4th usage, 44% of the dye decolorization capacity still could be achieved. These results are promising and suggest that bacteria-immobilized CA/PEO nanofibrous membrane could be economically feasible and eco-friendly when used in MB removal from industrial wastewater. Combination of both adsorption and biodegradation methods was found to be effective in MB removal from aqueous media.

Asunto(s)

Bacillus/metabolismo , Celulosa/análogos & derivados , Membranas Artificiales , Nanofibras/química , Polietilenglicoles/química , Aguas Residuales , Purificación del Agua , Adsorción , Bacillus/ultraestructura , Celulosa/química , Celulosa/ultraestructura , Azul de Metileno/aislamiento & purificación , Nanofibras/ultraestructura , Temperatura , Factores de Tiempo