Progesterone ameliorates diabetic nephropathy in streptozotocin-induced diabetic Rats

BACKGROUND: Previous studies reported that 17β-estradiol may influence the progression of diabetic renal disease in females. The present study was intended to provide an insight into the specific effects of progesterone, the other female sex hormone, in the diabetic renal complications. METHODS: Adult female wistar rats were divided into four groups (n = 6/group): intact control (non-diabetic, ND), intact diabetic (D), ovariectomized diabetic (D-OVX) and ovariectomized diabetic which were treated with progesterone (D-OVX + P; 10 mg/kg, s.c, every second day) for 10 weeks. Diabetes was induced by a single dose injection of 55 mg/kg streptozotocin. Expressions of transforming growth factor-β (TGF-β), fibronectin, vascular endothelial growth factor-A (VEGF-A), angiotensin II type 1 receptor (ATR1) and podocyte markers (nephrin and podocin) were assessed by immunohistochemistry and real-time PCR. RESULTS: The treatment of D-OVX rats with progesterone attenuated diabetic-associated increases in the urinary albumin to creatinine ratio, glomerulosclerosi and the expression of profibrotic and angiogenic factors (TGF-β, Fibronectin and VEGF-A). Furthermore, progesterone supplementation prevented diabetes-induced downregulation of nephrin and podocin while the overexpression of ATR1 in the diabetic rats was inhibited by the progesterone supplementation. CONCLUSION: These results provided evidence, for the first time, that the replacement of progesterone can ameliorate the renal damage in the experimental models of diabetic nephropathy through improving the renal function; the inhibition of renal fibrosis and abnormal angiogenesis; along with the amelioration of podocyte injury. Additionally, the blocking of renin-angiotensin system through the down-regulation of ATR1 expression may also account for the reno-protective effect of progesterone. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13098-015-0097-1) contains supplementary material, which is available to authorized users

Polish Adults’ Knowledge, Perceptions and Attitudes Concerning Legionellosis

Despite the growing prevalence of legionellosis in Poland and worldwide, little is known about the extent of public awareness regarding the seriousness of this disease and the appropriate preventive measures. The aim of this work is to assess the Polish adults’ knowledge, perceptions, and beliefs about legionellosis and its causative agents, risk factors, exposure, and other relevant facts. Data for this cross-sectional study were gathered via a questionnaire that was constructed and validated by the study investigators before commencing the survey, which lasted from January to March 2022. Knowledge, attitude and practice towards legionella were measured and quantified. One-way ANOVA and chi square tests were used to compare between demographic variables and the level of knowledge. Regression analysis was conducted to examine the predictors for higher knowledge among study participants. A total of 251 participants with a mean age of 28.26 ± 9.6 were enrolled in the current study. Over two thirds (74%) were females, with higher education (62%). Older age was associated with less knowledge about legionellosis (B = -0.049, p < 0.001), while higher education was associated with more knowledge (B = 1.656, p < 0.001). No significant differences were found between genders (p = 0.066). A knowledge gap was present for diagnostic tests regarding legionella. On the other hand, knowledge about prevention procedures was quite high among study participants. This study showed that overall knowledge about legionellosis in Polish adults was quite low. In particular, older age groups and the less educated are in need of more awareness of legionellosis disease. A knowledge gap was particularly present regarding how the disease is diagnosed. Awareness campaigns containing simple, easy-to-understand information could prove useful in combating the disease

Royal Jelly and Aliskiren mutually annul their protective effects against gentamicin-induced nephrotoxicity in rats

Background and Aim: Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained because of its nephrotoxic potential. Royal jelly (RJ) and aliskiren (ALK) can individually prevent such toxic effects. The aim of this study was to explore the protective effects of a combination treatment of RJ and ALK on GM-mediated nephrotoxicity. Materials and Methods: Thirty-two adult female Wistar rats were divided equally into four groups: (I) Receiving normal saline; (II) GM (100 mg/kg, intraperitoneal [i.p.] injection); (III) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection); and (IV) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection) in combination with RJ (150 mg/ kg, orally). All treatments were administered daily for 10 days. The blood levels of creatinine, urea, uric acid, albumin, and total protein were measured. Then, the animals were sacrificed, and the kidneys were taken for histopathology. Results: Compared to normal control rats, GM-injected rats showed significantly (p&lt;0.001) higher serum concentrations of uric acid, urea, and creatinine as well as evidently (p&lt;0.001) lower blood levels of albumin and total protein. Moreover, GM administration was associated with significant renal histopathological changes. All these alterations were considerably (p&lt;0.05) improved in GM-injected rats receiving ALK compared to rats receiving GM alone. However, when RJ was given in combination with ALK to GM-injected rats, it lessened the beneficial nephroprotective effects of both agents. Conclusion: The combination treatment of RJ and ALK is not desirable for GM-induced nephrotoxicity. Further studies are crucial to accurately explore the precise mechanism of RJ antagonistic interaction with ALK.</jats:p

Pharmacological repurposed agents for COVID-19

Coronavirus 2019 (COVID-19) pandemic has created a significant global challenge with respect to the search for specific and effective pharmacological agents with fewer adverse effects for treating this disease. To date, no effective therapy for COVID-19 has been established. Recent virological studies suggest an assortment of potential therapeutics, which could be good candidates for minimizing disease development. One of the most effective potential medications is Remdesivir, which has demonstrated in-vitro antiviral activity and is the first COVID-19 drug approved by the United States Food and Drug Administration (FDA). Adjunct medical care is used as an extra treatment method in addition to the essential treatment, for example, glucocorticoids, which cause a decline in the death rate in mechanically ventilated COVID-19 patients. More clinical preliminary studies should be conducted to explore the most effective pharmacological agent for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Numerous possible drug-drug interactions (DDIs) that may take place with the COVID-19 repurposed drugs and other medications have been identified. These facts might be beneficial for physicians to screen and identify potential DDIs with adverse consequences, and accordingly styling preventive and management approaches for their avoidance.</jats:p

Royal Jelly and Aliskiren mutually annul their protective effects against gentamicin-induced nephrotoxicity in rats

Background and Aim: Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained because of its nephrotoxic potential. Royal jelly (RJ) and aliskiren (ALK) can individually prevent such toxic effects. The aim of this study was to explore the protective effects of a combination treatment of RJ and ALK on GM-mediated nephrotoxicity. Materials and Methods: Thirty-two adult female Wistar rats were divided equally into four groups: (I) Receiving normal saline; (II) GM (100 mg/kg, intraperitoneal [i.p.] injection); (III) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection); and (IV) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection) in combination with RJ (150 mg/ kg, orally). All treatments were administered daily for 10 days. The blood levels of creatinine, urea, uric acid, albumin, and total protein were measured. Then, the animals were sacrificed, and the kidneys were taken for histopathology. Results: Compared to normal control rats, GM-injected rats showed significantly (p<0.001) higher serum concentrations of uric acid, urea, and creatinine as well as evidently (p<0.001) lower blood levels of albumin and total protein. Moreover, GM administration was associated with significant renal histopathological changes. All these alterations were considerably (p<0.05) improved in GM-injected rats receiving ALK compared to rats receiving GM alone. However, when RJ was given in combination with ALK to GM-injected rats, it lessened the beneficial nephroprotective effects of both agents. Conclusion: The combination treatment of RJ and ALK is not desirable for GM-induced nephrotoxicity. Further studies are crucial to accurately explore the precise mechanism of RJ antagonistic interaction with ALK

The Design and Anticancer Activity of a Citropin1.1 Hybrid Peptide with Selective Activity Against Highly Invasive Metastatic Cell Lines

Citropin 1.1 is an amphipathic alpha-helical cationic peptide that exhibits potent anticancer activity in vitro. Citropin 1.1 was found to be active against 60 cancer cell lines, and this activity was mainly attributed to its ability to bind and lyse membranes of cancer cells. One of the major drawbacks of developing Citropin 1.1 as an anticancer agent is its lack of apparent selectivity toward cancer cells and its ability to cause significant lysis of normal human erythrocytes and mammalian cells at high concentrations. This low selectivity index places severe restraints on the development of Citropin 1.1 as a novel anticancer agent. In this study, we have designed a Citropin 1.1 analog named Citropin A that retained the biological activity of the parent peptide. Citropin A was fused to an anionic fragment in order to neutralize the positive charge carried on the parent peptide rendering it inactive. The resultant hybrid peptide named Citropin-MMP was designed to contain a Matrix metalloproteinase (MMP) cleavable consensus sequence that would be cleaved to release the active Citropin A once it encounters highly metastatic MMP producing cancer cells. Citropin-MMP was found to be completely inactive against non-MMP producing cancer cells and normal mammalian cells. However, when Citropin-MMP was administered to MMP producing cells, its antiproliferative activity was regained, and the peptide displayed exclusive activity against MMP producing cancer cell lines. The data of our study indicate that this enzyme-based cleavage strategy could prove to be successful for the development of Citropin-MMP as a novel therapeutic agent for the purpose of inhibiting the proliferation and invasion of highly metastatic invasive cancer cells.</jats:p

Vitamin D as a drug: new therapeutic approaches

Vitamin D is one of the essential vitamins and has recently been demonstrated to be much more important for the appropriate functioning of the human body and well-being than initially believed. Although vitamin D is mainly known for its link with bone fractures and bone diseases, recent studies revealed that vitamin D and its analogues have revealed many pharmacological actions covering the regulation of cell growth, inhibition of inflammation, and improvement of neuromuscular function and immune function. Moreover, vitamin D and its analogues are reported to have role in different types of cancers, skin diseases, diabetes mellitus and infections caused by different bacterial and viral pathogens including SARS-CoV-2. The goal of this study is to evaluate the scientific literature on therapeutic uses of vitamin D and its analogues against different diseases and health condition. Special attention has been given to COVID-19 infection, cancer, skin diseases, and diabetes. The molecular mechanisms involved are also explored

A Novel EA-Based Techno&ndash;Economic Analysis of Charging System for Electric Vehicles: A Case Study of Qassim Region, Saudi Arabia

Because of the fast expansion of electric vehicles (EVs) in Saudi Arabia, a massive amount of energy will be needed to serve these vehicles. In addition, the transportation sector radiates a considerable amount of toxic gases in the form of SO2 and CO2. The national grid must supply a huge amount of electricity on a regular basis to meet the increasing power demands of EVs. This study thoroughly investigates the technical and economic benefits of an off-grid and grid-connected hybrid energy system with various configurations of a solar, wind turbine and battery energy storage system for the electric vehicle charging load in the Qassim region, Saudi Arabia. The goal is to decrease the cost of energy while reducing the chance of power outages in the system. This is achieved by using a new optimization algorithm called the modified salp swarm optimization algorithm (MSSOA), which is based on an evolutionary algorithm approach. MSSOA is an improved version of SSOA, which addresses its shortcomings. It has two search strategies to enhance its efficiency: first, it uses Levy flight distribution (LFD) to help individuals reach new positions faster, and second, it instructs individuals to spiral around the optimal solution, improving the exploitation phase. The MSSOA&rsquo;s effectiveness is confirmed by comparing its results with those of the conventional salp swarm optimization algorithm and particle swarm optimization (PSO). According to simulation findings, MSSOA has excellent accuracy and robustness. In this region, the SPV/WT/BESS-based EV charging station is the optimal option for EV charging stations. The SPV/WT/BESS design has the lowest LCOE of all feasible configurations in the region under study. The optimum values for the LCOE and TNPC using MSSOA are USD 0.3697/kWh and USD 99,928.34, which are much lower than the optimized values for the LCOE (USD 0.4156) and TNPC (USD 1,12,671.75) using SSOA. Furthermore, a comprehensive techno&ndash;economic analysis of optimized hybrid systems is assessed by incorporating the grid-connected option. The grid connected system results in optimized values of the LCOE (USD 0.0732/kWh) and TNPC (USD 1,541,076). The impact of different grid purchase prices on the levelized cost of energy is also studied. Our results will assist the researchers to determine the best technique for the optimization of an optimal energy system