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Sorafenib (SFB) is an anticancer drug with sparingly water solubility and reduced bioavailability. Nanoformulation of SFB can increase its dissolution rate and solubility. The current study aimed to formulate SFB in nanoparticles to improve their solubility. The sorafenib nanoparticles (SFB-PNs) were synthesized using the solvent evaporation method, then evaluated for their particle size, polydispersity index (PDI), zeta-potential, morphological structure, and entrapment efficiency (EE%). Further, the anticancer efficacy in A549 and Michigan Cancer Foundation-7 (MCF-7) cancer cell lines was evaluated. The SFB-NPs were uniform in size, which have 389.7 ± 16.49 nm, PDI of 0.703 ± 0.12, and zeta-potential of −13.5 ± 12.1 mV, whereas transmission electron microscopy showed a well-identified spherical particle. The EE% was found to be 73.7 ± 0.8%. SFB-NPs inhibited the cell growth by 50% after 48 h incubation, with IC50 of 2.26 and 1.28 µg/mL in A549 and MCF-7, respectively. Additionally, SFB-NPs showed a significant decrease (P < 0.05) in p21, and stathmin-1 gene expression levels in both cell lines. Moreover, SFB-NPs showed a significant increase in DNA damage of 25.50 and 26.75% in A549 and MCF-7, respectively. The results indicate that SFB-NPs are a potential candidate with an effective anticancer agent compared with free drugs.

Drug uptake and distribution through cell–receptor interactions are of prime interest in reducing the adverse effects and increasing the therapeutic effectiveness of delivered formulations. This study aimed to formulate silver nanoparticles (AgNPs) conjugated to somatostatin analogs for specific delivery through somatostatin receptors (SSTRs) expressed on cells and by nebulizing the prepared AgNPs formulations into lung cells for in vivo application. AgNPs were prepared using the citrate reduction method, yielding AgNPs–CTT, which was further chemically conjugated to octreotide (OCT) to form AgNPs–OCT through an amide linkage. The AgNPs–OCT formulation was coated using alginate to yield a carrier, AgNPs–OCT–Alg, feasible for drug delivery through nebulization. AgNPs were uniform in size with an acceptable range of zeta potential. Furthermore, the concentrations of AgNP formulations were found safe for the model cell lines used, and cell proliferation was significantly reduced in a dose-dependent manner (p < 0.05). In the healthy lung tissues, AgNPs–OCT–Alg accumulated at a concentration of 0.416 ± 5.7 mg/kgtissue, as determined via inductively coupled plasma optical emission spectrometry. This study established the accumulation of AgNPs, specifically the AgNPs–OCT–Alg, in lung tissues, and substantiated the active, specific, and selective targeting of SSTRs at pulmonary sites. The anticancer efficacy of the formulations was in vitro tested and confirmed in the MCF-7 cell lines. Owing to the delivery suitability and cytotoxic effects of the AgNPs–OCT–Alg formulation, it is a potential drug delivery formulation for lung cancer therapy in the future.

Background: We studied the potential of human bone marrow–derived mesenchymal stem cell conditioned media (hBMSC CM) in protecting endothelial cell properties (viability, proliferation, and migrations) from the deleterious effects produced by the inflammatory environment of H2O2. Additionally, we investigated their impact on the endothelial cells' gene expression of some inflammatory‐related genes, namely, TGF‐β1, FOS, ATF3, RAF‐1, and SMAD3. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured individually under three conditions: alone, with varying concentrations of H2O2, or with varying concentrations of H2O2 and hBMSC CM. HUVEC adhesion, proliferation, and migration were evaluated using the xCELLigence system. The HUVECs' gene expressions were evaluated by real‐time polymerase chain reaction (RT–PCR). Results: Generally, we observed enhanced HUVEC viability, proliferation, and migration when cultured in media supplemented with H2O2 and hBMSC CM. Furthermore, the CM modulated the expressions of the studied inflammatory‐related genes in HUVECs, promoting a more robust cellular response. Conclusion: This study has illuminated the protective role of hBMSC CM in mitigating the damaging effects of H2O2 on endothelial cell function. Our data demonstrate that hBMSC CM enhances the viability, proliferation, and migration of HUVECs even under oxidative stress conditions. Additionally, the conditioned medium was found to modulate the gene expression of pivotal markers related to inflammation, suggesting a favorable influence on cellular response mechanisms. [ABSTRACT FROM AUTHOR]

Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep‐G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF‐κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p‐AKT, PI3K, mTOR, NF‐κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF‐κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source. [ABSTRACT FROM AUTHOR]

Chemotherapeutic agents have numerous side effects. There is a major interest in using natural and safe plants as food or drink to prevent from cancer. Origanum marjoram (OMAE) is a medicinal plant that can be used as a tea, food, and additive in traditional medicine. This study aimed to evaluate the potential anticancer effects of OMAE as a soft drink for daily use against a model cancer, prevention and treatment. MCF-7 cells were chosen as model cancer cells. The MTT assay was used to assess the in vitro inhibitory effects of OMAE on cell growth. Moreover, quantitative real‐time PCR (qRT-PCR) was used to detect specific genes associated with cancer, such as ESR1, Bax, Bcl-2, and p53. Furthermore, the DNA damage was evaluated using the comet assay. OMAE has IC50 of 53.1 and IC90 of 97.5 μg/ml dependent inhibition of cell proliferation after 48 h of treatment toward MCF-7. Also, a significant decrease in the expression level of the ESR1 gene in the MCF-7 cell line. Furthermore, there was a significant increase in the comet length and comet-positive cells after treatment with OMAE (88.7%) compared with those in the untreated control cells (9.5%), suggesting a high induction of DNA damage by OMAE. Also, OMAE showed a modification in bcl-2, tumor suppressor gene (p53), and Bax levels and influenced the BAX/BCL-2 ratio via releasing the cytochrome C. The results of the study were promising, suggesting that the reduced apoptotic rate of MCF-7 breast cancer cells in this work was correlated to the potential anticancer effect of OMAE which would be a suitable preventable drink against cancer. However, further studies are needed to fully understand the potential of OMAE as a cancer treatment. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the phytochemical contents and antioxidant, antimicrobial, and antibiofilm activities of four halophytic plants, namely, Euphorbia chamaesyce, Bassia arabica, Fagonia mollis, and Haloxylon salicornicum, native to central Saudi Arabia. The alcoholic extract of E. chamaesyce was found to be the most potent in various bioactivities-based evaluations and rich in polyphenols and flavonoid secondary metabolites, with 68.0 mg/g and 39.23 mg/g gallic acid and quercetin equivalents, respectively. Among all plants' extracts, the alcoholic extract of E. chamaesyce had the highest DPPH scavenging and metal chelating antioxidant activities at 74.15 Trolox equivalents and 16.28 EDTA equivalents, respectively. The highest antimicrobial activity of E. chamaesyce extract was found to be against Shigella flexneri, with a mean zone of inhibition diameter of 18.1 ± 0.2 mm, whereas the minimum inhibitory concentration, minimum biocidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration values were 12.5, 25, 25, and 50 mg/mL, respectively. The LC-ESI-MS/MS analysis of the E. chamaesyce extract showed the presence of six flavonoids and ten phenolic constituents. The in silico binding of the E. chamaesyce extract's constituents to Staphylococcus aureus tyrosyl-tRNA synthetase enzyme displayed −6.2 to −10.1 kcal/mol binding energy values, suggesting that these constituents can contribute to the antimicrobial properties of the plant extract, making it an essential medicinal ingredient. In conclusion, these results warrant further investigation to standardize the antimicrobial profiles of these plant extracts. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF-α) and inflammatory cytokine (IL-6) play a vital role in various cellular incidents such as the proliferation and death of cells during carcinogenesis. Hence, regulation of these biomarkers could be a promising tool for controlling tumor progression using nanoformulations. Silver nanoparticles-poly (vinyl pyrrolidone) (AgNPs-PVP) were prepared using the reduction of silver nitrate and stabilized with PVP. They are characterized through yield percentage, UV-VIS, FT-IR, size, charge, and morphology. The obtained AgNPs were tested for anticancer activity against prostate cancer (PC 3) and human skin fibroblast (HFS) cell lines. Moreover, biomarker-based confirmations like TNF-α and IL-6 were estimated. The synthesized AgNPs-PVP were stable, spherical in shape, with particle sizes of 122.33 ± 17.61 nm, a polydispersity index of 0.49 ± 0.07, and a negative surface charge of −19.23 ± 0.61 mV. In vitro cytotoxicity testing showed the AgNPs-PVP exhibited antiproliferation properties in PC3 in a dose-dependent manner. In addition, when compared to control cells, AgNPs-PVP has lower TNF-α with a significant value ( ∗ p < 0.05); the value reached 16.84 ± 0.71 pg/ml versus 20.81 ± 0.44 pg/ml, respectively. In addition, HSF cells showed a high level of reduction ( ∗ ∗ ∗ p < 0.001) in IL-6 production. This study suggested that AgNPs-PVP could be a possible therapeutic agent for human prostate cancer and anti-IL-6 in cancerous and noncancerous cells. Further studies will be performed to investigate the effect of AgNPs-PVP in different types of cancer. [ABSTRACT FROM AUTHOR]

Urinary catheter infections remain an issue for many patients and can complicate their health status, especially for individuals who require long-term catheterization. Catheters can be colonized by biofilm-forming bacteria resistant to the administered antibiotics. Therefore, this study aimed to investigate the efficacy of silver nanoparticles (AgNPs) stabilized with different polymeric materials generated via a one-step simple coating technique for their ability to inhibit biofilm formation on urinary catheters. AgNPs were prepared and characterized to confirm their formation and determine their size, charge, morphology, and physical stability. Screening of the antimicrobial activity of nanoparticle formulations and determining minimal inhibitory concentration (MIC) and their cytotoxicity against PC3 cells were performed. Moreover, the antibiofilm activity and efficacy of the AgNPs coated on the urinary catheters under static and flowing conditions were examined against a clinical isolate of Escherichia coli. The results showed that the investigated polymers could form physically stable AgNPs, especially those prepared using polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC). Preliminary screening and MIC determinations suggested that the AgNPs-EC and AgNPs-PVP had superior antibacterial effects against E. coli. AgNPs-EC and AgNPs-PVP inhibited biofilm formation to 58.2% and 50.8% compared with AgNPs-PEG, silver nitrate solution and control samples. In addition, coating urinary catheters with AgNPs-EC and AgNPs-PVP at concentrations lower than the determined IC50 values significantly (p < 0.05; t-test) inhibited bacterial biofilm formation compared with noncoated catheters under both static and static and flowing conditions using two different types of commercial Foley urinary catheters. The data obtained in this study provide evidence that AgNP-coated EC and PVP could be useful as potential antibacterial and antibiofilm catheter coating agents to prevent the development of urinary tract infections caused by E. coli. [ABSTRACT FROM AUTHOR]

Objective: We determined the efficacy of self-administered subcutaneous mini-dose glucagon (MDG) to treat fasting-induced hypoglycemia in type 1 diabetes (T1D).Research Design and Methods: This was a 4-week randomized, controlled crossover trial of 2-week MDG or 2-week oral glucose tablets (OG, control) involving 17 adults with T1D during Ramadan.Results: Compared with OG, MDG demonstrated a significant higher change in blood glucose from baseline to 30 min (Δt30, P < 0.001) and 1 h (Δt60, P = 0.02). The efficacy of MDG was preserved following ≥8 h fasting with significantly higher Δt30 in MDG (P = 0.01). Over the entire 2 weeks, MDG period had increased time in 70-180 mg/dL (P = 0.009) and less time <70 mg/dL (P = 0.04). MDG use resulted in higher completion of fasts compared with OG (P < 0.001).Conclusions: MDG administration is an effective alternative to OG for prevention and treatment of fasting-induced hypoglycemia, offering improved glycemic control and promoting successful completion of prolonged fasts. [ABSTRACT FROM AUTHOR]

Background. The benefits of prescribing statins are well published in the treatment of hypercholesterolemia. With such widespread usage of statins, physicians may be ignoring or misdiagnosing the association of oral side effects with these medications. Case Summary. A 54-year-old man presented with a painful ulceration on the dorsum of his tongue that had been recurring for 10 months. Originally, he experienced a burning sensation on his tongue, and as the lesion advanced, the pain became more intense specially when consuming spicy or acidic foods. He is on rosuvastatin for the treatment of hypercholesterolemia for over five years. Several months prior to the lesion forming, his physician increased his daily dosage of rosuvastatin from 10 mg to 20 mg. Four weeks later at a follow-up appointment, all workup did not show any significant findings, the examination revealed a new ulcer on the dorsum of the tongue, and he reported no improvement after antifungal lozenges, nor when administered a short one-week treatment with oral steroids. After eight weeks of statin discontinued, the patient showed improvement with no episodes of ulceration. Conclusion. Physicians do note that statins affect multiple immunological pathways, which could explain some adverse cutaneous reactions. More research is needed in discovering the link of statins and oral disorders. [ABSTRACT FROM AUTHOR]

The treatment of breast cancer requires long chemotherapy management, which is accompanied by severe side effects. Localized delivery of anticancer drugs helps to increase the drug concentration at the site of action and overcome such a problem. In the present study, chitosan hydrogel was prepared for local delivery of 5-Fluorouracil. The in vitro release behavior was investigated and the anticancer activity was evaluated against MCF-7 cells using MTT assay. The in vivo studies were investigated via intra-tumoral injection of a 5-FU loaded hydrogel into breast cancer of female rats. The results indicated that the modified hydrogel has excellent physicochemical properties with a sustained in vitro release profile matching a zero-order kinetic for one month. In addition, the hydrogel showed superior inhibition of cell viability compared with the untreated control group. Moreover, the in vivo studies resulted in antitumor activity with minor side effects. The tumor volume and level of tumor markers in blood were inhibited significantly by applying the hydrogel compared with the untreated control group. In conclusion, the designed injectable hydrogels are potential drug delivery systems for the treatment of breast cancer with a controlled drug release profile, which could be suitable for decreasing the side effects of chemotherapy agents. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress, lipid profile and renal functions are well-known conventional risk factors for diabetes mellitus (DM). Metformin and gliclazide are popularly used monotherapy drugs for the treatment of DM. Aims: This study aims to assess the short-term treatment of single and dual therapy of glipizide/metformin on oxidative stress, glycemic control, serum lipid profiles and renal function in diabetic rats. Methods: DM was induced in rats with streptozotocin (STZ), then five different treatments were applied, including group I (untreated healthy control), group II (diabetic and untreated), group III (diabetic and treated with metformin), group IVI (diabetic and treated with glipizide) and group V (diabetic and treated with a combination of metformin and glipizide. Lipid peroxidation (LPO), nitric oxide (NO), total antioxidant capacity (TAC), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and urea were measured. Results: Compared to the untreated DM group, FBG and HbA1c were significantly reduced in the DM groups (p < 0.01) treated with metformin (159.7 mg/dL & 6.7%), glipizide (184.3 mg/dL & 7.3%) and dual therapy (118 mg/dL & 5.2%), respectively. Treatment with dual therapy and metformin significantly decreased LPO and NO levels but increased TAC in diabetic rats more than glipizide compared to untreated diabetic rats. Furthermore, metformin (19.8 mg/dL, p < 0.001), glipizide (22.7 mg/dL, p < 0.001), and dual therapy (25.7 mg/dL, p < 0.001) significantly decreased urea levels in the treated rats compared to untreated DM rats (32.2 mg/dL). Both drugs and their combination exhibited a substantial effect on total cholesterol, HDL, LDL and atherogenic index. Conclusions: These results suggest that the therapeutic benefits of metformin and glipizide are complementary. Metformin exhibited superior performance in improving glycemic control and decreasing oxidative stress, while glipizide was more effective against dyslipidemia. These findings could be helpful for the treatment of future vascular patients, antilipidemic medicines and antioxidant therapy to improve the quality of life. [ABSTRACT FROM AUTHOR]

Allium cepa L (A. cepa) extract is frequently used as an adjuvant food in cancer treatment. We hypothesized that it contains a source of anticancer activity. There is a need to synthesize the silver nanoparticles (AgNPs) using an environment-friendly green synthesis reduction method using an aqueous extract of A. cepa. The AgNPs-CEPA were prepared by reduction method using the aqueous extract of A. cepa. The formed AgNPs-CEPA were characterized for their sizes and charge distribution. The AgNP-CEPA was investigated for its antioxidant and anticancer properties. Cell viability was evaluated by MTT assay. Gene expression was evaluated by real-time polymerase chain reaction (RT-PCR), and apoptosis measurement was carried out by flow cytometry in AgNP-CEPA-treated cells. The results showed a uniform size for AgNPs-CEPA of 155 ± 2.1 nm with a zeta potential of − 37.3 ± − 2.92 mv. The produced AgNPs-CEPA are biocompatible with anticancer action and a moderate level of antioxidant reactivity. AgNPs-CEPA showed better reducing activity for A. cepa extract compared to the AgNPs-CEPA. AgNP-CEPA treatment of human colorectal cancer cell lines (HT-29 and SW620) inhibited cell proliferation and altered Bcl2 family gene expression. Moreover, exposure of cell lines to AgNPs-CEPA resulted in the significant induction of apoptosis compared to A. cepa and AgNO3. These findings indicate that AgNP-CEPA induces apoptosis by inhibiting Bcl2 family gene expression, suggesting that this formula is a promising anticancer agent for treating colorectal cancer. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the anti breast-cancer activity, biocompatibility and toxicity of poly(d,l)-lactic-co-glycolic acid (PLGA)-encapsulated quercetin nanoparticles (Q-PLGA-NPs). Materials & methods: Quercetin was nano-encapsulated by an emulsion–diffusion process, and the nanoparticles were fully characterized through Fourier transform infrared spectroscopy, x-ray diffractions, FESEM and zeta-sizer analysis. Activity against CAL51 and MCF7 cell lines were assessed by DNA fragmentation assays, fluorescence microscopy, and acridine-orange, and propidium-iodide double-stainings. Biocompatibility towards red blood cells and toxicity towards mice were also explored. Results: The Q-PLGA-NPs exhibited apoptotic activity against the cell lines. The murine in vivo studies showed no significant alterations in the liver and kidney's functional biomarkers, and no apparent abnormalities, or tissue damages were observed in the histological images of the liver, spleen, lungs, heart and kidneys. Conclusion: The study established the preliminary in vitro efficacy and in vivo safety of Q-PLGA-NPs as a potential anti-breast cancer formulation. Quercetin is a flavonoid, a type of chemical, antioxidant in nature, found in many fruits and vegetables. It is known to have anticancer properties. In this study, quercetin was encased into nano-sized particles of biologically compatible and bio-degradable synthetic polymer, named PLGA (poly-[D,L]-lactic-co-glycolic acid). The effects of the quercetin nanoparticles/nano-quercetin were tested against two types of breast cancer cell lines in the laboratory. The quercetin-loaded nanoparticles were able to kill the breast cancer cells, suggesting they could be able to kill the cancer cells in the body. Also, when given to mice, the quercetin nanoparticles did not appear to damage any organ, or change the functions of the liver, and kidneys, thereby suggesting that they are not toxic. Further work is required to assess how well they could be used to treat breast cancer in people. [ABSTRACT FROM AUTHOR]

Background: Gentamicin (GM) is an antibiotic that is widely used to treat many Gram-negative bacteria, such as those involved in urinary tract infections. However, being nephrotoxic, GM dose adjustment and reno-protective elements must be concurrently administered with GM to minimize kidney damage. Oxidative stress plays a pivotal role in the pathogenesis of GM-induced nephrotoxicity. Thymoquinone (TQ) is a promising therapeutic substance, that is being extensively studied in many diseases, such as diabetes mellitus, cancer, hypertension, and others. The powerful antioxidant properties of TQ may greatly help in minimizing GM nephrotoxicity. Metformin (MF) is a well-known, clinically approved oral hypoglycaemic drug that has many other actions, including antioxidant properties. The aim of this work was to evaluate the possible antioxidant and reno-protective effects of TQ and metformin in GM-induced nephrotoxicity in the same model (rats) at the same time. In addition, we aimed to further understand the effects underlying GM-induced nephrotoxicity. Methods: Twenty male rats were randomly divided into four equal groups: the first group (control) received distilled water; the second group received GM only; the third group received concurrent oral TQ and GM; and the fourth group received concurrent oral MF and GM. After 4 weeks, renal function and histopathology, as well as levels of the oxidative markers glutathione peroxidase-1 (GLPX1), superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissues, were assessed. Results: Compared with the control group, and as expected, the GM-injected rats showed significant biochemical and histological changes denoting renal damage. Compared with GM-injected rats, the concurrent administration of TQ with GM significantly reduced the levels of serum creatinine, serum urea, and tissue MDA and significantly increased the levels of GLPX1 and SOD. Concurrent metformin administration with GM significantly increased the levels of both GLPX1 and SOD and significantly decreased the levels of tissue MDA but had no significant effect on serum creatinine and urea levels. Compared with GM-injected rats, the addition of either TQ or MF resulted in a reduction in endothelial proliferation and mesangial hypercellularity. Conclusions: Both TQ and MF effectively alleviated the oxidative stress in GM-induced nephrotoxicity in rats, with TQ but not MF producing a complete reno-protective effect. Further studies for evaluation of different reno-protective mechanisms of TQ should be conducted. [ABSTRACT FROM AUTHOR]

Purpose: Blood transfusion is a conventional therapeutic procedure; however, the perceptions of general public and healthcare professionals (HCPs), especially physicians and nurses, remain unclear, although the insights of HSPs may affect the treatment decision. This study aimed to assess the awareness of HCPs and the public about blood transfusion risks and consent in Qassim region of Saudi Arabia, to uncover the factors that may influence such perceptions. Patients and Methods: This study used two different closed questionnaires that were distributed electronically between February and March 2018 among the population and HCPs in Qassim region. Results: A total of 400 general public participants and 135 HCPs completed the survey. Among the surveyed participants, 70% believed that blood transfusion therapy was safe. The perceived risk of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) was the highest among all complications (74%). Furthermore, 88.2% of respondents were willing to accept a blood transfusion as a therapeutic measure, primarily from a first-degree relative, although the remaining 11.8% rejected the idea of a transfusion due to fear of medical error. From the HCP survey, 80% were previously involved in a blood transfusion therapy consent process. HCPs typically reported explaining the benefits, risks, and alternatives described in the consent form (74.1%, 67.4%, and 53.3%, respectively). Conclusion: Our results indicated that despite the current high level of acceptance and knowledge regarding blood transfusions, additional educational efforts remain necessary to increase public awareness of blood transfusion therapy. [ABSTRACT FROM AUTHOR]

Background: Murraya koenigii leaves are traditionally used in India and other South Asian countries as a spice in regular food dishes to improve taste and aroma. These leaves are known for the rich content of mahanimbine, a key carbazole alkaloid. Although there are numerous reports that support the neuroprotective role of various alkaloids, the effect of mahanimbine against memory impairment remains to be elucidated. Objective: The present study aimed to explore the neuroprotective potential of mahanimbine against lipopolysaccharides (LPS)-induced memory deficit in Institute of Cancer Research (ICR) mice. Materials and Methods: Group of mice were being fed with mahanimbine (1, 2, and 5 mg/kg, p. o.) for 30 days. Subsequently, neuroinflammation was induced with LPS (250 μg/kg, i. p.) for 4 days. Morris water maze (MWM) assessment was conducted to assess spatial memory. The brain was then collected and subjected to amyloid-beta (Aβ) (Aβ1-42and Aβ1-40) measurement, acetylcholine (ACh) and acetylcholinesterase (AChE) assays and neuroinflammatory analyses (interleukin [IL]-1 β, tumor necrosis factor alpha [TNF-α], IL-10 transforming growth factor beta [TGF-β], and cyclooxygenase [COX]). Results: The MWM test showed that treatment with mahanimbine significantly enhanced memory of LPS-challenged mice by decreasing both escape latency as well as escape distance. Pretreatment of the LPS-challenged mice with mahanimbine improved central cholinergic transmission by increasing ACh level through inhibition of AChE. It also significantly attenuated Aβ1-40level. While anti-inflammatory cytokines (TGF-β and IL-10) were upregulated, mahanimbine significantly inhibited pro-inflammatory cytokines (IL-1 β and TNF-α), the total activity of COX, and expression of COX-2 gene in LPS-induced group. Conclusion: The overall findings supported the neuroprotective potential of mahanimbine against LPS-induced neuroinflammation. [ABSTRACT FROM AUTHOR]

Background Type 2 diabetes is a chronic condition that requires pharmacotherapy interventions. Metformin and gliclazide are widely used drugs in monotherapy. However, their complementary action made utilization of the combination of these drugs an appealing approach. Aims The study compared major therapeutic potentials of combined metformin/gliclazide treatment over metformin monotherapy based on the following parameters: oxidative stress, lipid profile, and hepatorenal functions. Subjects and methods This is a comparative study was conducted from March 2015 to March 2016. The study screened 80 type 2 diabetic patients, of which 40 patients underwent combined metformin + gliclazide therapy (500 mg BD + 80 mg OD, respectively). The other 40 were matched for age and duration of diabetes mellitus with the previous group and received metformin monotherapy (500 mg BD). The levels of fasting blood glucose (FBG), total glycated hemoglobin (HbA1c), lipid peroxidation, total antioxidant capacity, serum creatinine, aspartate and alanine transaminases, total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were measured according to the standard methods. Results Oxidative stress, lipid profile, and hepatorenal functions were comparable in patients of both groups. However, patients on metformin treatment showed significantly lower levels of FBG [7.61 (6.70–8.89) mmol/L vs. 9.00 (7.30–10.68) mmol/L; P = .022] and HBA1c [7.00 (6.40–7.65)% vs. 8.20 (7.20–9.75)%; P < .001] compared to those on combined therapy. Conclusion Oxidative stress, lipids profile, and hepatorenal functions were not different in patients who were on combined metformin/gliclazide therapy and compared to those metformin alone. In contrast, glycemic control was poor in the diabetic patients undergoing combined therapy. [ABSTRACT FROM AUTHOR]

Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS). Anticancer drug etoposide (ETP) was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP) and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes) and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes). The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs. [ABSTRACT FROM AUTHOR]

The present study assessed serum miR-15b, Annexin A1, procalcitonin, and interleukin-6 (IL-6) levels in children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and compared them to these levels in a non-obese healthy control group. It also tested the ability of each of these parameters to early differentiate children with MUO from those with MHO. The present study included 620 children [434 males (70%) and 186 females (30%); aged 9-15 years] divided into the following groups: G1, healthy non-obese controls (n=200); G2, MHO (n=246); G3, MUO (n=174). Serum miR-15b, Annexin A1 procalcitonin, IL-6, and other metabolic parameters levels were measured, and clinical examinations were conducted for all of the children. After testing the normality of the variable, Kruskal-Wallis one-way-ANOVA, and Spearman correlation coefficients were used. The area under the receiver operating characteristic curve (AUC) was determined to test the variable's ability to differentiate MUO from MHO. miR-15b, procalcitonin, and IL-6 levels were significantly higher while Annexin A1 levels were significantly lower in G2 and G3 when compared to G1, and in G3 when compared to G2. These levels were positively correlated (Annexin A1 was negatively correlated) with body mass index (BMI) and waist circumference percentiles, and with serum levels of LDL-cholesterol, glucose, HbA1c, insulin, and C-reactive protein (CRP) and with the homeostasis model of insulin resistance (HOMA-IR). The AUC was 0.92, 0.84, 0.82, and 0.67 for miR-15b, Annexin A1, procalcitonin, and IL-6, respectively. In conclusion, determination of serum miR-15b, Annexin A1, and procalcitonin levels could differentiate children with MUO from those with MHO. This may help the early management of these cases and their accompanying complications. [ABSTRACT FROM AUTHOR]

Four halophytic plants, Lycium shawii, Anabasis articulata, Rumex vesicarius, and Zilla spinosa, growing in the central Qassim area, Saudi Arabia, were phytochemically and biologically investigated. Their hydroalcoholic extracts' UPLC-ESIQ-TOF analyses demonstrated the presence of 44 compounds of phenolic acids, flavonoids, saponins, carbohydrates, and fatty acids chemical classes. Among all the plants' extracts, L. shawii showed the highest quantities of total phenolics, and flavonoids contents (52.72 and 13.01 mg/gm of the gallic acid and quercetin equivalents, respectively), along with the antioxidant activity in the TAA (total antioxidant activity), FRAP (ferric reducing antioxidant power), and DPPH-SA (2,2-diphenyl-1-picryl-hydrazyl-scavenging activity) assays with 25.6, 56.68, and 19.76 mg/gm, respectively, as Trolox equivalents. The hydroalcoholic extract of the L. shawii also demonstrated the best chelating activity at 21.84 mg/gm EDTA equivalents. Among all the four halophytes, the hydroalcoholic extract of L. shawii exhibited the highest antiproliferative activity against MCF7 and K562 cell lines with IC50 values at 194.5 µg/mL and 464.9 µg/mL, respectively. The hydroalcoholic extract of A. articulata demonstrated better cytotoxic activity amongst all the tested plants' extracts against the human pancreatic cancer cell lines (PANC1) with an IC50 value of 998.5 µg/mL. The L. shawii induced apoptosis in the MCF7 cell lines, and the percentage of the necrotic cells changed to 28.1% and 36.5% for the IC50 and double-IC50 values at 22.9% compared with the untreated groups. The hydroalcoholic extract of L. shawii showed substantial antibacterial activity against Bacillus cereus ATCC 10876 with a MIC value of 12.5 mg/mL. By contrast, the A. articulata and Z. spinosa exhibited antifungal activities against Aspergillus niger ATCC 6275 with MIC values at 12.5 and 50 mg/mL, respectively. These findings suggested that the L. shawii is a potential halophyte with remarkable biological properties, attributed to its contents of phenolics and flavonoid classes of compounds in its extract. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the short-term effects of Thymoquinone (TQ) on oxidative stress, glycaemic control, and renal functions in diabetic rats. DM was induced in groups II and III with a single dose of streptozotocin (STZ), while group I received no medication (control). The rats in groups I and II were then given distilled water, while the rats in group III were given TQ at a dose of 50 mg/kg body weight/day for 4 weeks. Lipid peroxidase, nitric oxide (NO), total antioxidant capacity (TAC), glycated haemoglobin (HbA1c), lipid profiles, and renal function were assessed. Moreover, the renal tissues were used for histopathological examination. STZ increased the levels of HbA1c, lipid peroxidase, NO, and creatinine in STZ-induced diabetic rats in comparison to control rats. TAC was lower in STZ-induced diabetic rats than in the control group. Furthermore, rats treated with TQ exhibited significantly lower levels of HbA1c, lipid peroxidase, and NO than did untreated diabetic rats. TAC was higher in diabetic rats treated with TQ than in untreated diabetic rats. The histopathological results showed that treatment with TQ greatly attenuated the effect of STZ-induced diabetic nephropathy. TQ effectively adjusts glycaemic control and reduces oxidative stress in STZ-induced diabetic rats without significant damaging effects on the renal function. [ABSTRACT FROM AUTHOR]

Zygophyllum coccineum, an edible halophytic plant, is part of the traditional medicine chest in the Mediterranean region for symptomatic relief of diabetes, hypertension, wound healing, burns, infections, and rheumatoid arthritis pain. The current study aimed to characterize Z. coccineum phytoconstituents, and the evaluations of the anti-microbial-biofilm, and anti-cancers bioactivities of the plant's mother liquor, i.e., aqueous-ethanolic extract, and its subsequent fractions. The in silico receptors interaction feasibility of Z. coccineum major constituents with Staph GyraseB, and human topoisomerase-IIβ (h-TOP-IIβ) were conducted to confirm the plant's anti-microbial and anti-cancer biological activities. Thirty-eight secondary metabolites of flavonoids, stilbene, phenolic acids, alkaloids, and coumarin classes identified by LC-ESI-TOF-MS spectrometric analysis, and tiliroside (kaempferol-3-O-(6′′′′-p-coumaroyl)-glucoside, 19.8%), zygophyloside-F (12.78%), zygophyloside-G (9.67%), and isorhamnetin-3-O-glucoside (4.75%) were identified as the major constituents. A superior biofilm obliteration activity established the minimum biofilm eradication concentration (MBEC) for the chloroform fraction at 3.9–15.63 µg/mL, as compared to the positive controls (15.63–31.25 µg/mL) against all the microbial strains that produced the biofilm under study, except the Aspergillus fumigatus. The aqueous-ethanolic extract showed cytotoxic effects with IC50 values at 3.47, 3.19, and 2.27 µg/mL against MCF-7, HCT-116, and HepG2 cell-lines, respectively, together with the inhibition of h-TOP-IIβ with IC50 value at 45.05 ng/mL in comparison to its standard referral inhibitor (staurosporine, IC50, 135.33 ng/mL). This conclusively established the anti-cancer activity of the aqueous-ethanolic extract that also validated by in silico receptor-binding predicted energy levels and receptor-site docking feasibility of the major constituents of the plant's extract. The study helped to authenticate some of the traditional phytomedicinal properties of the anti-infectious nature of the plant. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a chronic progressive disease that portends a very poor prognosis. It has been suggested that STAT3 is a potential target in PF. This study highlights the importance of cubosomes as a drug delivery system in enhancing the bioavailability of nifuroxazide (NXZD), a poorly soluble STAT3 inhibitor. NXZD-loaded cubosomes (NXZD-LC) were in vitro and in vivo evaluated. In vitro, cubosomes presented a poly-angular nanosized particles with a mean size and zeta potential of 223.73 ± 4.73 nm and − 20.93 ± 2.38 mV, respectively. The entrapment efficiency of nifuroxazide was 90.56 ± 4.25%. The in vivo pharmacokinetic study and the lung tissue accumulation of NXZD were performed by liquid chromatography-tandem mass spectrometry after oral administration to rats. The nanoparticles exhibited a two-fold increase and 1.33 times of bioavailability and lung tissue concentration of NXZD compared to NXZD dispersion, respectively. In view of this, NXZD-LC effectively attenuated PF by targeting STAT3 and NF-κB signals. As a result, NXZD-LC showed a potential anti-inflammatory effect as revealed by the significant decrease in MCP-1, ICAM-1, IL-6, and TNF-α and suppressed fibrogenic mediators as indicated by the significant reduction in TGF-β, TIMP-1, and PDGF-BB in lung tissues. Besides, NXZD-LC improved antioxidant defense mechanisms and decreased LDH and BALF total protein. These effects contributed to decreased collagen deposition. To conclude, cubosomes represent an advantageous pharmaceutical delivery system for enhancing pulmonary delivery of poorly soluble drugs. Additionally, repurposing NXZD as an antifibrotic agent is a promising challenge and new therapeutic approach for unmet therapeutic needs. [Display omitted] • Pulmonary fibrosis is a progressive disease that portends a very poor prognosis. • Nifuroxazide, an antibiotic, is a poorly soluble STAT3 inhibitor. • Nifuroxazide cubosomes exhibited advancement in bioavailability and lung delivery. • Nifuroxazide cubosomes exhibited anti-inflammatory and antifibrotic potential. • Nifuroxazide repurposing as an antifibrotic agent is a promising challenge. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is one the most common causes of morbidity and mortality in critically ill patients. In this study, we examined for first time the role of dapagliflozin (DPGZ) in lipopolysaccharide (LPS)-induced ALI in rats and determined the underlying molecular mechanisms by evaluating the effects of DPGZ on adenosine monophosphate kinase (AMPK), nuclear transcription factor kappa B, nucleotide-binding and oligomerization domain-like receptor 3 inflammasome activation. Treatment of acute lung injured rats with either low dose (5 mg/kg) or high dose (10 mg/kg) DPGZ significantly decreased oxidative stress by decreasing malondialdehyde and nitric oxide tissue levels with a significant increase in spectrophotometric measurements of superoxide dismutase, catalase, and reduced glutathione levels. DPGZ treatment resulted in a significant anti-inflammatory effect as indicated by suppression in myeloperoxidase activity, MCP-1, IL-1β, IL-18, and TNF-α levels. DPGZ treatment also increased p-AMPK/t-AMPK with a significant reduction in NF-kB P65 binding activity and NFĸB p65 (pSer536) levels. These effects of DPGZ were accompanied by a significant reduction in NLRP3 levels and NLRP3 gene expression and a significant decrease in caspase-1 activity, which were also confirmed by histopathological examinations. We conclude that DPGZ antioxidant and anti-inflammatory activity may occur through regulation of AMPK/NFĸB pathway and inhibition of NLRP3 activation. These results suggest that DPGZ represents a promising intervention for the treatment of ALI, particularly in patients with type 2 diabetes. • AMPK/NFκB and NLRP3 interplay is a new therapeutic target in inflammation. • Dapagliflozin mitigated lipopolysaccharide-mediated lung injury. • Dapagliflozin anti-inflammatory effects were mediated through AMPK/NFĸB regulation. • Dapagliflozin inhibited NLRP3 inflammasome and caspase-1 activity. [ABSTRACT FROM AUTHOR]

Background: We studied the potential of human bone marrow-derived mesenchymal stem cell conditioned media (hBMSC CM) in protecting endothelial cell properties (viability, proliferation, and migrations) from the deleterious effects produced by the inflammatory environment of H 2 O 2 . Additionally, we investigated their impact on the endothelial cells' gene expression of some inflammatory-related genes, namely, TGF- β 1, FOS, ATF3, RAF-1, and SMAD3. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured individually under three conditions: alone, with varying concentrations of H 2 O 2 , or with varying concentrations of H 2 O 2 and hBMSC CM. HUVEC adhesion, proliferation, and migration were evaluated using the xCELLigence system. The HUVECs' gene expressions were evaluated by real-time polymerase chain reaction (RT-PCR). Results: Generally, we observed enhanced HUVEC viability, proliferation, and migration when cultured in media supplemented with H 2 O 2 and hBMSC CM. Furthermore, the CM modulated the expressions of the studied inflammatory-related genes in HUVECs, promoting a more robust cellular response. Conclusion: This study has illuminated the protective role of hBMSC CM in mitigating the damaging effects of H 2 O 2 on endothelial cell function. Our data demonstrate that hBMSC CM enhances the viability, proliferation, and migration of HUVECs even under oxidative stress conditions. Additionally, the conditioned medium was found to modulate the gene expression of pivotal markers related to inflammation, suggesting a favorable influence on cellular response mechanisms., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Abdulmajeed Alqasoumi et al.)

Liver fibrosis is a disease with a great global health and economic burden. Existing data highlights itraconazole (ITRCZ) as a potentially effective anti-fibrotic therapy. However, ITRCZ effect is hindered by several limitations, such as poor solubility and bioavailability. This study aimed to formulate and optimize chitosan nanoparticles (Cht NPs) loaded with ITRCZ as a new strategy for managing liver fibrosis. ITRCZ-Cht NPs were optimized utilizing a developed 2 2 full factorial design. The optimized formula (F3) underwent comprehensive in vitro and in vivo characterization. In vitro assessments revealed that F3 exhibited an entrapment efficiency of 89.65% ± 0.57%, a 169.6 ± 1.77 nm particle size, and a zeta potential of +15.93 ± 0.21 mV. Furthermore, in vitro release studies indicated that the release of ITRCZ from F3 adhered closely to the first-order model, demonstrating a significant enhancement ( p-value < 0.05) in cumulative release compared to plain ITRCZ suspension. This formula increased primary hepatocyte survival and decreased LDH activity in vitro . The in vivo evaluation of F3 in a rat model of liver fibrosis revealed improved liver function and structure. ITRCZ-Cht NPs displayed potent antifibrotic effects as revealed by the downregulation of TGF-β, PDGF-BB, and TIMP-1 as well as decreased hydroxyproline content and α-SMA immunoexpression. Anti-inflammatory potential was evident by reduced TNF-α and p65 nuclear translocation. These effects were likely ascribed to the modulation of Hedgehog components SMO, GLI1, and GLI2. These findings theorize ITRCZ-Cht NPs as a promising formulation for treating liver fibrosis. However, further investigations are deemed necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elmorsy, Saber, Kira, Alghasham, Abdel-Hamed, Amer, Mohamed, AlSalloom A., Alkhamiss, Hamad, Abdel-Reheim, Ellethy, Elsisi, Alsharidah, Elghandour, Elnawawy and Abdelhady.)

β-Blockers have been one of the most widely used and versatile drugs for the past half a century. A new potential for their use as anti-cancer drugs has emerged in the past few years. Various retrospective case control studies have been suggestive that use of β-blockers before the diagnosis of cancer could have preventive and protective effects against non-small cell lung carcinoma, melanoma, and breast, pancreatic and prostate cancers. Experimental and clinical observations are still inconclusive with some inconsistent findings. However, indications are pointing toward a positive role of some β-blockers against certain forms of cancers. This mini review is an effort to present the up to date published results of case-control studies and experimental findings.