Mechanistic insights and in vivo efficacy of thiosemicarbazones against methicillin-resistant Staphylococcus aureus.

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) represents 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.

Bisphenol-A exposure alters liver, kidney, and pancreatic Klotho expression by HSP60-activated mTOR/autophagy pathway in male albino rats.

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.

Fortification of Fermented Camel Milk with Salvia officinalis L. or Mentha piperita Leaves Powder and Its Biological Effects on Diabetic Rats.

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.

Apoptotic susceptibility of pancreatic alpha cells to environmentally relevant dose levels of bisphenol-A versus dibutyl phthalate is mediated by HSP60/caspase-3 expression in male albino rats.

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.

Expression and clinical significance of SNAI1 and ZEB1 genes in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, it represents nearly 32% of all new cases of leukemia. This study aimed to evaluate the SNAI1 and ZEB1 genes expression in AML patients and determine their diagnostic and prognostic significance. We determined the expression of SNAI1 and ZEB1 genes and serum E-cadherin levels in early diagnosed patients with AML. Sixty early diagnosed AML patients and 20 healthy subjects were enrolled in this study, SNAI1 and ZEB1 genes expression was determined by Real-time PCR while E-Cadherin serum levels were determined by ELISA. The results of this study demonstrated that, all AML patients positively expressed the SNAI1 gene with fold change 2.6. While, the ZEB1 expression was positive in 56.7% of the patients with fold change 1.8. SNAI1 and ZEB1 genes were highly expressed in M5 subtype (FC = 13.8 and 9.3, respectively). On the other hand, serum E-cadherin concentrations of the AML patients showed decrease when compared with those of the control but the decrease was not reach to the significance level. The findings of this study suggest inclusion of SNAI1 and ZEB1 genes expression in the cluster of potential genetic biomarkers to be studied in AML cases as diagnostic and prognostic markers.

Sex-specific endocrine-disrupting effects of three halogenated chemicals in Japanese medaka.

Several halogenated chemicals are found in an array of products that can cause endocrine disruption. Human studies have shown that endocrine responses are sex specific, with females more likely to develop hypothyroidism and males more likely to have reproductive impairment. The objective of this study was to assess sex differences on thyroid and estrogenic effects after exposure of Japanese medaka (Oryzias latipes, SK2MC) to halogenated compounds. This strain is an excellent model for these studies as sex can be determined non-destructively a few hours postfertilization. Medaka embryos were exposed to sublethal concentrations of Tris(1,3-dichloro-2-propyl) phosphate (TDCPP, 0.019 mg/L), perfluorooctanoic acid (PFOA, 4.7 mg/L) and its next generation alternative, perfluorobutyric acid (PFBA, 137 mg/L). Methimazole (inhibits thyroid hormone synthesis) and the thyroid hormone triiodothyronine served as reference controls. Fish were exposed throughout embryo development until 10 days postfertilization. Females displayed significantly larger swim bladders (which are under thyroid hormone control) after exposure to all chemicals with the exception of triiodothyronine, which caused the opposite effect. Females exposed to TDCPP and PFOA had increased expression of vitellogenin and exposure to PFOA upregulated expression of multiple thyroid-related genes. Upregulation of estrogenic-regulated genes after exposure to TDCPP, PFOA and methimazole was only observed in males. Overall, our results suggest that females and males show an estrogenic response when exposed to these halogenated chemicals and that females appear more susceptible to thyroid-induced swim bladder dysfunction compared with males. These results further confirm the importance of considering sex effects when assessing the toxicity of endocrine-disrupting compounds.

Dose-response relationship between sulfonylureas and major adverse cardiovascular events in elderly patients with type 2 diabetes.

PURPOSE: The objective of this study was to determine if there is a dose-response relationship between sulfonylureas and major adverse cardiovascular events (MACE). METHODS: We conducted a retrospective cohort study among elderly patients with no history of acute coronary syndrome or stroke who initiated gliclazide or glyburide therapy between 1998 and 2010. Gliclazide and glyburide users were evaluated separately, and a high-dimensional propensity score (HDPS) was used to match patients initiating therapy with a low or high dose. A time-dependent variable was used to further characterize exposure, which can change during follow-up. Cox proportional hazard regression models were used to compare the risk of MACE between low (reference) and high doses. RESULTS: We identified 14,213 new users of gliclazide or glyburide (mean age, 74.7 (standard deviation 6.4) years; males, 52.8%; and mean follow-up duration, 2.7 (standard deviation 2.9) years). Among gliclazide users, there was a higher risk of MACE with high compared with low dose (crude rates: 32.8 and 28.2 per 1000 person-years, respectively), but this did not reach statistical significance (HDPS-matched hazard ratio) 1.15; 95% confidence interval (0.96-1.38). For glyburide users, however, MACE occurred more frequently in the high compared with low dose (crude rates: 38.9 and 31.5 per 1000 person-years, respectively; HDPS-matched hazard ratio 1.24; 95% confidence interval 1.02-1.50). CONCLUSIONS: Among new users of sulfonylureas, there appears to be a dose-response relationship between glyburide and MACE, but not for gliclazide. Copyright © 2016 John Wiley & Sons, Ltd.

A zebrafish-based acoustic motor response (AMR) assay to evaluate chemical-induced developmental neurotoxicity.

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.

Effects of developmental exposure to arsenic species on behavioral stress responses in larval zebrafish and implications for stress-related disorders.

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.

Effects of developmental exposure to individual and combined PFAS on development and behavioral stress responses in larval zebrafish.

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.

Assessing the effects of fluorine-free and PFAS-containing firefighting foams on development and behavioral responses using a zebrafish-based platform.

Significant progress has been made in developing fluorine-free firefighting foams (F3) as alternatives to perfluoroalkyl substances (PFAS)-containing aqueous film-forming foams (AFFF) to help eliminate the health and environmental concerns linked to PFAS exposure. However, developing viable F3 options hinges on a thorough assessment of potential risks alongside the technical performance evaluations. This study showcases the capability of a zebrafish-based platform to discern the developmental and behavioral toxicities associated with exposure to one AFFF and two F3 formulations. To facilitate direct exposure to the chemicals, embryos were enzymatically dechorionated and then exposed to the diluted formulations (6-120 hours post fertilization (hpf)) at concentrations folding from 0.1% of the manufacturer-recommended working concentrations. The exposure regimen also included daily automated media changes (50%) and mortality assessments (24 and 120 hpf). At 120 hpf, a comprehensive assessment encompassing overall development, prevalence of morphological defects, and behavioral responses to acute stressors (visual, acoustic, and peripheral irritant) was conducted. Exposure to both F3s significantly increased larval mortalities to percentages exceeding 90%, whereas AFFF exposures did not cause any significant effect. Overall development, marked by total larval length, was significantly impacted following exposures to all foams. Behavioral responses to acute stressors were also significantly altered following exposures to both F3s, whereas the AFFF did not alter behavior at the concentrations tested. Our findings demonstrate toxicities associated with tested F3 formulations that encompass several endpoints and highlight the utility of the proposed platform in evaluating the developmental toxicities of current and future foam formulations.

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) as markers of active lupus nephritis.

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.

Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress.

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.

Pirfenidone targeted mechanisms for alleviating methotrexate-induced testiculopathy in Wistar rats.

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.

Internet of Things (IoT) for Soil Moisture Tensiometer Automation.

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.

Initial assessment of the toxicologic effects of leachates from 3-dimensional (3-D) printed objects on sperm quality in two model fish species.

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.

ACE2/ACE imbalance mediates bisphenol A-induced lung injury in Wistar rats: Results from captopril versus losartan histo-biochemical study.

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.

Modeling the Effects of Cypermethrin Toxicity on Ovalbumin-Induced Allergic Pneumonitis Rats: Macrophage Phenotype Differentiation and p38/STAT6 Signaling Are Candidate Targets of Pirfenidone Treatment.

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.

Poncet's disease: An uncommon presentation of a common disease in Sudan.

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.

Histomorphological Changes in a Rat Model of Polycystic Ovary Syndrome and the Contribution of Stevia Leaf Extract in Modulating the Ovarian Fibrosis, VEGF, and TGF-ß Immunoexpressions: Comparison with Metformin.

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.