Bridging the gap: glucose transporters, Alzheimer's, and future therapeutic prospects.

Glucose is the major source of chemical energy for cell functions in living organisms. The aim of this mini-review is to provide a clearer and simpler picture of the fundamentals of glucose transporters as well as the relationship of these transporters to Alzheimer's disease. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic databases (PubMed and ScienceDirect) were used to search for relevant studies mainly published during the period 2018-2023. This mini-review covers the two main types of glucose transporters, facilitated glucose transporters (GLUTs) and sodium-glucose linked transporters (SGLTs). The main difference between these two types is that the first type works through passive transport across the glucose concentration gradient. The second type works through active co-transportation to transport glucose against its chemical gradient. Fluctuation in glucose transporters translates into a disturbance of normal functioning, such as Alzheimer's disease, which may be caused by a significant downregulation of GLUTs most closely associated with insulin resistance in the brain. The first sign of Alzheimer's is a lack of GLUT4 translocation. The second sign is tau hyperphosphorylation, which is caused by GLUT1 and 3 being strongly upregulated. The current study focuses on the use of glucose transporters in treating diseases because of their proven therapeutic potential. Despite this, studies remain insufficient and inconclusive due to the complex and intertwined nature of glucose transport processes. This study recommends further understanding of the mechanisms related to these vectors for promising future therapies.

Itraconazole Loaded Biosurfactin Micelles with Enhanced Antifungal Activity: Fabrication, Evaluation and Molecular Simulation.

Itraconazole (ITZ) is a broad-spectrum antifungal for superficial subcutaneous and systemic fungal infections. This study aimed to enhance the antifungal activity of ITZ using surfactin A (SA), a cyclic lipopeptide produced by the SA-producing Bacillus strain NH-100, possessing strong antifungal activity. SA was extracted, and ITZ-loaded SA micelles formulations were prepared via a single-pot rinsing method and characterized by particle size, zeta potential, and infrared spectroscopy. In vitro dissolution at pH 1.2, as well as hemolysis studies, was also carried out. The fabricated formulations were stable and non-spherical in shape, with an average size of about 179 nm, and FTIR spectra depicted no chemical interaction among formulation components. ITZ-loaded micelles showed decreased hemolysis activity in comparison to pure ITZ. The drug released followed the Korsmeyer-Peppas model, having R2 0.98 with the diffusion release mechanism. In an acidic buffer, drug release of all prepared formulations was in the range of 73-89% in 2 h. The molecular simulation showed the outstanding binding and stability profile of the ITZ-SA complex. The aromatic ring of the ITZ mediates a π-alkyl contact with a side chain in the SA. It can be concluded that ITZ-loaded micelles, owing to significant enhanced antifungal activity up to 6-fold due to the synergistic effect of SA, can be a promising drug delivery platform for delivery of poorly soluble ITZ.

Cu-doped mesoporous TiO2 photocatalyst for efficient degradation of organic dye via visible light photocatalysis.

A solvothermal method was used to synthesize the mesoporous TiO2, (1-3w %) Cu-doped mesoporous TiO2 membrane with the help of a bioreactor. To understand the physicochemical composition of all synthesized nanomaterials, the structure, morphology and crystallinity of the materials were studied using X-ray diffractometer (XRD), Field emission scanning electron microscopy (FESEM), Fourier transform-infrared (FTIR), Energy dispersive X-ray spectroscopy (EDS) and cyclic voltammetry (CV). Under artificial light source (500 W mercury bulb) irradiations, the nano catalysts' catalytic effectiveness was examined for the azo dyes, namely Congo red. Cu-doping causes a shift in the light absorption of mTiO2 from the ultraviolet to the visible region. The 3w% Cu-doped mTiO2 photocatalyst exhibits lower band gap energy (2.6eV) than TiO2 which is 3.2 eV to efficiently utilize solar energy. As a result, the light absorption was shifted towards the visible spectrum. The recommended mTiO2 and (1, 2, 3) w% Cu-doped mTiO2 photocatalysts were used to photodegrade Congo red and methylene blue. For the degradation of CR, the mTiO2 photocatalyst exhibited 61% and 3w% Cu-doped mTiO2 demonstrated 99% photocatalytic performance after 50 min. A variety of scavengers were also utilized to distinguish the active species by catching the radicals and holes created during the process of photocatalytic degradation. CV indicates the presence of Cu2+ and Cu1+ in Cu-doped mTiO2. Oxygen vacancies and the electronegative surface of Cu1+ seem to perform the photocatalytic reduction of CR.

Immediate and contributory causes of death in patients hospitalized with COVID-19.

OBJECTIVES: Accurate determination of the immediate causes of death in patients with COVID-19 is important for optimal care and mitigation strategies. METHODS: All deaths in Qatar between March 01, 2020, and August 31, 2022, flagged for likely relationship to COVID-19 were reviewed by two independent, trained reviewers using a standardized methodology to determine the immediate and contributory causes of death. RESULTS: Among 749 flagged deaths, the most common admitting diagnoses were respiratory tract infection (91%) and major adverse cardiac event (MACE, 2.3%). The most common immediate causes of death were COVID-19 pneumonia (66.2%), MACE (7.1%), hospital-associated pneumonia (HAP, 6.8%), bacteremia (6.3%), disseminated fungal infection (DFI, 5.2%), and thromboembolism (4.5%). After COVID-19 pneumonia, MACE was the predominant cause of death in the first 2 weeks but declined thereafter. No death occurred due to bacteremia, HAP, or DFI in the first week after hospitalization, but became increasingly common with increased length of stay in the hospital accounting for 9%, 12%, and 10% of all deaths after 4 weeks in the hospital, respectively. CONCLUSION: Nearly one-third of patients with COVID-19 infection die of non-COVID-19 causes, some of which are preventable. Mitigation strategies should be instituted to reduce the risk of such deaths.

Evaluation of mortality attributable to SARS-CoV-2 vaccine administration using national level data from Qatar.

Accurate determination of mortality attributable to SARS-CoV-2 vaccination is critical in allaying concerns about their safety. We reviewed every death in Qatar that occurred within 30 days of any SARS-CoV-2 vaccine administration between January 1, 2021 and June 12, 2022. Probability of association with SARS-CoV-2 vaccination was determined by four independent trained reviewers using a modified WHO algorithm. Among 6,928,359 doses administered, 138 deaths occurred within 30 days of vaccination; eight had a high probability (1.15/1,000,000 doses), 15 had intermediate probability (2.38/1,000,000 doses), and 112 had low probability or no association with vaccination. The death rate among those with high probability of relationship to SARS-CoV-2 vaccination was 0.34/100,000 unique vaccine recipients, while death rate among those with either high or intermediate probability of relationship to SARS-CoV-2 vaccination was 0.98/100,000 unique vaccine recipients. In conclusion, deaths attributable to SARS-CoV-2 vaccination are extremely rare and lower than the overall crude mortality rate in Qatar.

Energy, exergy, economic, environment, exergo-environment based assessment of amine-based hybrid solvents for natural gas sweetening.

Natural gas is the cleanest form of fossil fuel that needs to be purified from CO2 and H2S to diminish harmful emissions and provide feasible processing. The conventional chemical and physical solvents used for this purpose have many drawbacks, including corrosion, solvent loss, high energy requirement, and the formation of toxic compounds, which ultimately disrupt the process and affect the environment. Hybrid solvents have lately been researched to cater to these liabilities and enhance process economics. This study screened eight solvents based on CO2 selectivity viscosity, absorption enthalpy, corrosivity, working capacity, specific heat, and vapor pressure. From the screened solvents, ten cases of hybrid solvents are simulated and optimized on Aspen HYSYS®. Furthermore, 5Es (Energy, Exergy, Economic, Environmental, and Exergy-environmental) analyses were performed on optimized cases, and results were compared with the base case, MEA (30 wt%). The hybrid blend of Sulfolane and MDEA with weight percentages of 6% and 24%, respectively, showed the highest energy savings of 20% concerning the base case. In addition, it offered 93% savings in exergy destruction and 17.26% in the total operating cost of the process. It is also promising to the environment due to reduced entropy sent to the ecosystem and controlled CO2 emissions. Therefore, the blend of Sulfolane and MDEA is proposed to Supersede the conventional solvent MEA for the natural gas sweetening process.

Prevalence of coronavirus disease 2019 in a multiethnic cohort of patients with autoimmune rheumatic diseases in Qatar.

BACKGROUND: Autoimmune rheumatic diseases (ARDs) are characterized by immune dysfunction and associated with an increased risk of infections, which were of significant concern during the coronavirus disease 2019 (COVID-19) pandemic. Variable rates of COVID-19 incidence have been reported in patients with ARDs; however, the true effect of this infection on this patient population is still unclear. We, therefore, aimed to evaluate the COVID-19 prevalence among a multiethnic cohort of patients with ARDs in Qatar. MATERIAL AND METHODS: We used telephonic surveys to collect demographic and clinical information of patients with ARD in Qatar between April 1 and July 31, 2020, including any close contact with a COVID-19 case at home or work and polymerase chain reaction (PCR)-confirmed COVID-19 diagnosis. An electronic medical records review was conducted to verify pertinent data collected through the surveys. Prevalence with 95% confidence interval (CI), Student's t-tests, and chi-square/Fisher's exact tests were used for univariate analyses, whereas multivariate logistic regression was used to identify factors associated with COVID-19. RESULTS: The study included 700 patients with ARD (mean age, 43.2 ± 12.3 years), and 73% were female. Until July 2020, 75 (11%, 95% CI 9%-13%) patients had COVID-19. Factors associated with COVID-19 included being a man (adjusted odds ratio [aOR] 2.56, 95% CI 1.35-4.88, p = 0.01) and having close contact with a COVID-19 case (aOR 27.89, 95% CI 14.85-52.38, p = 0.01). Disease severity and rheumatic medications had no significant association with the odds of contracting COVID-19. In the 86 patients with ARD having close contact, the frequency of hydroxychloroquine utilization was lower in patients who contracted COVID-19 than in those who did not (35% vs 72.5%, p = 0.01). CONCLUSIONS: In Qatar, patients with ARDs had an overall higher prevalence of COVID-19 than global estimates. Being male and having close contact with a COVID-19 case were strongly associated with COVID-19 as reported globally. The presence of comorbid conditions, disease-specific factors, and rheumatic medications had no significant effect on the risk of COVID-19 in our study suggesting alternative mechanisms to the increased prevalence.

Green Synthesis of Silver Nanoparticles Using Thespesia populnea Bark Extract for Efficient Removal of Methylene Blue (MB) Degradation via Photocatalysis with Antimicrobial Activity and for Anticancer Activity.

The green synthesis method was used to effectively fabricate Ag-NPs by using Thespesia populnea bark extract. The structural, morphological, elemental composition, and optical properties of as-synthesized Ag-NPs were characterized by powder X-ray diffraction (P-XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDAX), transmission electron microscopy (TEM), and UV-Vis spectroscopy. Their photocatalytic efficiency as a photocatalyst was examined by degradation of methylene blue (MB) dye under direct sunlight irradiation. After 120 minutes of sunlight irradiation, Ag-NPs show photocatalytic degradation efficiency (DE percent) of 92%. The hydroxyl and superoxide radicals were found to be responsible for biodegradation. To the best of our acquaintance, this is the first research to use Ag-NPs as a photocatalyst for the efficient degradation of MB dye and its antimicrobial activity by using Thespesia populnea bark extract. The cytotoxic viability against SK-MEL cell line with a median inhibitory concentration (IC50) of 45 µL/mg proved its potent anticancer property. Based on the findings, the study revealed the significance of as-synthesized green Ag-NPs over other physically/chemically prepared Ag-NPs.

Nanoelectroablation therapy for murine basal cell carcinoma.

When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1(+/-)K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology [2,20] and in response to drug therapy [19]. We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 ± 5 (SEM) mm(3) shrunk by 76 ± 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

Optimized nanosecond pulsed electric field therapy can cause murine malignant melanomas to self-destruct with a single treatment.

We have identified a new, nanosecond pulsed electric field (nsPEF) therapy capable of eliminating murine melanomas located in the skin with a single treatment. When these optimized parameters are used, nsPEFs initiate apoptosis without hyperthermia. We have developed new suction electrodes that are compatible with human skin and have applied them to a xenograft nude mouse melanoma model system to identify the optimal field strength, pulse frequency and pulse number for the treatment of murine melanomas. A single treatment using the optimal pulse parameters (2,000 pulses, 100 ns in duration, 30 kV/cm in amplitude at a pulse frequency of 5-7 pulses/sec) eliminated all 17 melanomas treated with those parameters in 4 mice. This was the highest pulse frequency that we could use without raising the treated skin tumor temperature above 40 degrees C. We also demonstrate that the effects of nsPEF therapy are highly localized to only cells located between electrodes and results in very little scarring of the nsPEF-treated skin.

A new pulsed electric field therapy for melanoma disrupts the tumor's blood supply and causes complete remission without recurrence.

We have discovered a new, ultrafast therapy for treating skin cancer that is extremely effective with a total electric field exposure time of only 180 microsec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec) electrical pulses to murine melanomas in vivo triggers both necrosis and apoptosis, resulting in complete tumor remission within an average of 47 days in the 17 animals treated. None of these melanomas recurred during a 4-month period after the initial melanoma had disappeared. These pulses generate small, long-lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting in increased membrane permeability to small molecules and ions, as well as an increase in intracellular Ca(2+), DNA fragmentation, disruption of the tumor's blood supply and the initiation of apoptosis. Apoptosis was indicated by a 3-fold increase in Bad labeling and a 72% decrease in Bcl-2 labeling. In addition, microvessel density within the treated tumors fell by 93%. This new therapy utilizing nanosecond pulsed electric fields has the advantages of highly localized targeting of tumor cells and a total exposure time of only 180 microsec. These pulses penetrate into the interior of every tumor cell and initiate DNA fragmentation and apoptosis while at the same time reducing blood flow to the tumor. This new physical tumor therapy is drug free, highly localized, uses low energy, has no significant side effects and results in very little scarring.