A novel equation for the estimation of low-density lipoprotein cholesterol in the Saudi Arabian population: a derivation and validation study.

Low-density lipoprotein cholesterol (LDL-C) is typically estimated by the Friedewald equation to guide atherosclerotic cardiovascular disease (ASCVD) management despite its flaws. Martin-Hopkins and Sampson-NIH equations were shown to outperform Friedewald's in various populations. Our aim was to derive a novel equation for accurate LDL-C estimation in Saudi Arabians and to compare it to Friedewald, Martin-Hopkins and Sampson-NIH equations. This is a cross-sectional study on 2245 subjects who were allocated to 2 cohorts; a derivation (1) and a validation cohort (2). Cohort 1 was analyzed in a multiple regression model to derive an equation (equationD) for estimating LDL-C. The agreement between the measured (LDL-CDM) and calculated levels was tested by Bland-Altman analysis, and the biases by absolute error values. Validation of the derived equation was carried out across LDL-C and triglyceride (TG)-stratified groups. The mean LDL-CDM was 3.10 ± 1.07 and 3.09 ± 1.06 mmol/L in cohorts 1 and 2, respectively. The derived equation is: LDL-CD = 0.224 + (TC × 0.919) - (HDL-C × 0.904) - (TG × 0.236) - (age × 0.001) - 0.024. In cohort 2, the mean LDL-C (mmol/L) was estimated as 3.09 ± 1.06 by equationD, 2.85 ± 1.12 by Friedewald, 2.95 ± 1.09 by Martin-Hopkins, and 2.93 ± 1.11 by Sampson-NIH equations; statistically significant differences between direct and calculated LDL-C was observed with the later three equations (P < 0.001). Bland-Altman analysis showed the lowest bias (0.001 mmol/L) with equationD as compared to 0.24, 0.15, and 0.17 mmol/L with Friedewald, Martin-Hopkins, and Sampson-NIH equations, respectively. The absolute errors in all guideline-stratified LDL-C categories was the lowest with equationD, which also showed the best classifier of LDL-C according to guidelines. Moreover, equationD predicted LDL-C levels with the lowest error with TG levels up to 5.63 mmol/L. EquationD topped the other equations in estimating LDL-C in Saudi Arabians as it could permit better estimation when LDL-C is < 2.4 mmol/L, in familial hyperlipidemia, and in hypertriglyceridemia, which improves cardiovascular outcomes in high-risk patients. We recommend further research to validate equationD in a larger dataset and in other populations.

RETRACTED: Alhakamy et al. Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells. Pharmaceutics 2020, 12, 761.

The journal retracts the article, "Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells" [...].

RETRACTED: Awan et al. The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells. Pharmaceutics 2020, 12, 597.

The journal retracts the article, "The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells" [...].

RETRACTED: Alhakamy et al. Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells. Pharmaceutics 2020, 12, 346.

The journal retracts the article, "Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells" [...].

In silico exploration of the potential inhibitory activities of in-house and ZINC database lead compounds against alpha-glucosidase using structure-based virtual screening and molecular dynamics simulation approach.

Inhibitors of α-glucosidase have been used to treat type-2 diabetes (T2DM) by preventing the breakdown of carbohydrates into glucose and prevent enhancing glucose conversion. Structure-based virtual screening (SBVS) was used to generate novel chemical scaffold-ligand α-glucosidase inhibitors. The databases were screened against the receptor α-glucosidase using SBVS and molecular dynamics simulation (MDS) techniques in this study. Based on molecular docking studies, three and two compounds of α-glucosidase inhibitors were chosen from a commercial database (ZINC) and an In-house database for this study respectively. The mode of binding interactions of the selected compounds later predicted their α-glucosidase inhibitory potential. Finally, one out of three lead compound from ZINC and one out of two lead compound from In-house database were shortlisted based on interactions. Furthermore, MDS and post-MDS strategies were used to refine and validate the shortlisted leads along with the reference acarbose/α-glucosidase. The Hits' ability to inhibit α-glucosidase was predicted by SBVS, indicating that these compounds have good inhibitory activities. The lead inhibitor's structure may serve as templates for the design of novel inhibitors, and in vitro testing to confirm their anti-diabetic potential is necessary. These insights can help rationally design new effective anti-diabetic drugs.Communicated by Ramaswamy H. Sarma.

RETRACTED: Ahmed et al. Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route. Nanomaterials 2020, 10, 1270.

The Journal retracts the article "Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route" [...].

Green synthesis of silver nanoparticles from plant Fagonia cretica and evaluating its anti-diabetic activity through indepth in-vitro and in-vivo analysis.

One of the most widespread metabolic diseases, Type-2 Diabetes Mellitus (T2DM) is defined by high blood sugar levels brought on by decreased insulin secretion, reduced insulin action, or both. Due to its cost-effectiveness and eco-friendliness, plant-mediated green synthesis of nanomaterials has become more and more popular. The aim of the study is to synthesize AgNPs, their characterizations and further in-vitro and in-vivo studies. Several methods were used to morphologically characterise the AgNPs. The AgNPs were crystalline, spherical, and clustered, with sizes ranging from 20 to 50 nm. AgNPs were found to contain various functional groups using Fourier transform infrared spectroscopy. This study focuses on the green-synthesis of AgNPs from Fagonia cretica (F. cretica) leaves extract to evaluate their synthesized AgNPs for in-vitro and in-vivo anti-diabetic function. For the in-vivo tests, 20 male Balb/C albino-mice were split up into four different groups. Anti-diabetic in-vivo studies showed significant weight gain and a decrease in all biochemical markers (pancreas panel, liver function panel, renal function panel, and lipid profile) in Streptozotocin (STZ)-induced diabetic mice. In vitro anti-diabetic investigations were also conducted on AgNPs, comprising α-amylase, α-glucosidase inhibitions, and antioxidant assays. AgNPs showed antioxidant activity in both the DPPH and ABTS assays. The research showed that the isolated nanoparticles have powerful antioxidant and enzyme inhibitory properties, especially against the main enzymes involved in T2DM.

Optimizing Eco-Friendly Degradation of Polyvinyl Chloride (PVC) Plastic Using Environmental Strains of Malassezia Species and Aspergillus fumigatus.

Worldwide, huge amounts of plastics are being introduced into the ecosystem, causing environmental pollution. Generally, plastic biodegradation in the ecosystem takes hundreds of years. Hence, the isolation of plastic-biodegrading microorganisms and finding optimum conditions for their action is crucial. The aim of the current study is to isolate plastic-biodegrading fungi and explore optimum conditions for their action. Soil samples were gathered from landfill sites; 18 isolates were able to grow on SDA. Only 10 isolates were able to the degrade polyvinyl chloride (PVC) polymer. Four isolates displayed promising depolymerase activity. Molecular identification revealed that three isolates belong to genus Aspergillus, and one isolate was Malassezia sp. Three isolates showed superior PVC-biodegrading activity (Aspergillus-2, Aspergillus-3 and Malassezia) using weight reduction analysis and SEM. Two Aspergillus strains and Malassezia showed optimum growth at 40 °C, while the last strain grew better at 30 °C. Two Aspergillus isolates grew better at pH 8-9, and the other two isolates grow better at pH 4. Maximal depolymerase activity was monitored at 50 °C, and at slightly acidic pH in most isolates, FeCl3 significantly enhanced depolymerase activity in two Aspergillus isolates. In conclusion, the isolated fungi have promising potential to degrade PVC and can contribute to the reduction of environmental pollution in eco-friendly way.

In-depth in-vitro and in-vivo anti-diabetic evaluations of Fagonia cretica mediated biosynthesized selenium nanoparticles.

Therapeutic moieties derived from medicinal plants as well as plants-based ecofriendly processes for producing selenium nanoparticles have shown great promise in the management of type 2 diabetes mellitus (T2DM). The current study was aimed to assess the anti-diabetic potentials of Fagonia cretica mediated biogenic selenium nanoparticles (FcSeNPs) using in-vitro and in-vivo approaches. The bio-synthesized FcSeNPs were characterized using various techniques including UV-VIS spectrophotometry and FTIR analysis. The in-vitro efficacy of FcSeNPs were assessed against α-glucosidase, α-amylase enzymes as well as the anti-radical studies were performed using DPPH and ABTS free radicals scavenging assays. For in-vivo studies, 20 Male Balb/C albino-mice were randomly divided into 4 groups (n = 5) including normal group, disease group (Diabetic group with no treatment), control group and treatment group (Diabetic group treated with FcSeNPs). Further, biochemistry markers including pancreas, liver, kidney and lipid profile were assessed for all treatment groups. The FcSeNPs exhibited a dose-dependent inhibition against α-amylase and α-glucosidase at 62-1000 µg mL-1 concentration with IC50 values of 92 and 100 µg mL-1 respectively. In antioxidant experiments, the FcSeNPs demonstrated significant radicals scavenging effect against DPPH and ABTS radicals. In STZ-induced diabetic mice, a considerable decline in blood glucose level was observed after treatment with FcSeNPs. Anti-hyperglycemic effect of FcSeNPs treated animals were high (105 ± 3.22**) as compared to standard drug (128.6 ± 2.73** mg dL-1). Biochemical investigations revealed that all biochemical parameters for pancreas, liver function, renal function panel and lipid profile were significantly lowered in FcSeNPs treated animals. Our findings indicate a preliminary multi-target efficacy for FcSeNPs against type-2 diabetes and thus warrant further detailed studies.

Blood indices of omega-3 and omega-6 polyunsaturated fatty acids are altered in hyperglycemia.

Polyunsaturated fatty acids (PUFAs) may favorably influence the risk and clinical course of diabetes mellitus (DM). In particular, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) alleviate oxidative injury and insulin resistance characteristic of DM. Uncertainty still remains, however, as to the composition and proportions of blood PUFAs in relation to fasting blood glucose levels. This study, thus, aims to examine the patterns of blood PUFA indices in normoglycemic (NG) and hyperglycemic (HG) Saudi subjects. Age, gender, FA profiles, and laboratory records of 143 subjects collected from September 2014 to March 2018 were retrospectively analyzed. Means, prevalence rates, associations, risk measures, and the diagnostic accuracy of PUFAs were determined. HG subjects had significantly lower AA (0.70%, 95% CI: 0.59-0.80% vs 0.46%, 95% CI: 0.38-0.53%) and higher EPA/AA ratio (0.36, 95% CI: 0.30-0.42 vs 0.69, 95% CI: 0.61-0.77). Gender-wise comparisons revealed that ώ-6/ώ-3 ratio was the only PUFA index significantly elevated in HG males (0.36, 95% CI: 0.26-0.45 vs 5.68, 95% CI: 4.98-6.38) while both DHA (2.91%, 95% CI: 2.54-3.29% vs 3.37%, 95% CI: 3.13-3.60%) and ώ-3 index (3.1%, 95% CI: 2.70-3.49% vs 3.63%, 95% CI: 3.38-3.88%) were significantly elevated in HG females. Furthermore, reduced AA and elevated EPA/AA ratio were more prevalent in HG subjects (26.53 vs 28.72 and 30.61 vs 38.29, respectively) and exhibited the highest diagnostic accuracy for HG among all PUFA indices. Altogether, our study revealed that distinct, gender-specific blood PUFA indices are differentially regulated in HG subjects which may be valuable for DM management.

Patterns of 25-Hydroxyvitamin D3, Calcium Status, and Anemia in the Saudi Population: A Cross-Sectional Study.

BACKGROUND: Emerging evidence suggests an intricate relationship between vitamin D, Ca2+, and inflammation-driven anemia. We, thus, investigated the patterns of serum 25(OH)D3, Ca2+, ferritin, and iron in healthy and anemic members of the Saudi population. METHODS: A population-based, retrospective, cross-sectional study was designed to analyze data for 14,229 subjects, aged 3-110 years, obtained from Al-Borg Medical Laboratories, over a six-year period (2014-2020). Gender and age differences were analyzed for 25(OH)D3, Ca2+, hemoglobin, ferritin, and iron. RESULTS: Vitamin D deficiency was extremely prevalent (98.47%) irrespective of age or gender, despite an increasing trend with age, in clear contrast to serum Ca2+. Ferritin was significantly lower in young adult and adult females, compared to elderly females, whereas iron was significantly reduced in females; in particular, adult females compared to young adults or elderly adults. Only anemic adult males had significantly lower 25(OH)D3, while Ca2+ was consistently significantly diminished in anemics of all age groups, independent of gender. Notably, hypocalcemic subjects were 2.36 times more likely to be anemic. Moreover, ferritin, but not iron, was significantly diminished in anemics, which was only evident in young adults and adults. However, both ferritin and iron showed positive correlation with hematocrit, hemoglobin, MCH, MCHC, and MCV. CONCLUSIONS: Despite being significantly lower in anemics, 25(OH)D3 is not particularly associated with anemia, while hypocalcemia is associated with an increased risk for anemia. Assessment of vitamin D and Ca2+ status may be valuable in the clinical management of anemia in the Saudi population.

Monocyte-Lymphocyte Ratio and Dysglycemia: A Retrospective, Cross-Sectional Study of the Saudi Population.

Background: Abnormalities in fasting blood glucose (FBG) resulting in hypoglycemia (OG), impaired fasting glycemia (IFG), or hyperglycemia (HG) arise from disordered metabolic regulation caused in part by inflammation. To date, there is a dearth of evidence regarding the clinical utility of the monocyte−lymphocyte ratio (MLR), an emerging inflammatory index, in the management of dysglycemia. Methods: This retrospective, cross-sectional study explored MLR fluctuations as a function of glycemic control in 14,173 Saudi subjects. Data collected from 11 August 2014 to 18 July 2020 were retrieved from Al-Borg Medical Laboratories. Medians were compared by Mann−Whitney U or Kruskal−Wallis tests and the prevalence, relative risk (RR), and odds ratio (OR) were calculated. Results: MLR was significantly elevated in IFG (p < 0.0001) and HG (p < 0.05) groups compared to the normoglycemia (NG) group, and individuals with elevated MLR (>0.191) had significantly increased FBG (p < 0.001). The risk of IFG (RR = 1.12, 95% CI: 1.06−1.19, p < 0.0002) and HG (RR = 1.10, 95% CI: 1.01−1.20, p < 0.0216) was significantly increased if MLR was elevated, and individuals with elevated MLR were 1.17 times more likely to have IFG (OR = 1.17, 95% CI: 1.08−1.26, p < 0.0002) and 1.13 times more likely to have HG (OR = 1.13, 95% CI: 1.02−1.24, p < 0.0216). Conclusion: Elevated MLR is correlated with and carries a greater risk for IFG and HG. However, large prospective cohort studies are needed to establish the temporal relationship between MLR and FBG and to examine the prognostic value of this novel marker.

Patterns of Dyslipidemia in the Anemic and Nonanemic Hypertensive Saudi Population: A Cross-Sectional Study.

Background: Risk factors of cardiovascular disease include dyslipidemia, hypertension (HTN), and anemia. Our objective is to assess the patterns of dyslipidemia in the anemic and non-anemic hypertensive Saudi population. Methods: A retrospective, cross-sectional study of the gender, blood pressure, lipid markers, and CBC parameters of 3111 subjects, which were retrieved from the database of Al-Borg Medical Laboratories over a six-year period (2014-2019), was carried out. Means were compared among study groups and the prevalence, association, and diagnostic accuracy of lipid markers for HTN were evaluated. Results: TG, LDL/HDL, and TG/HDL were significantly higher (P < 0.0001) in hypertensives. Anemia reduces TC and LDL (P < 0.0001) in both genders, and reduces all markers and increases HDL (P < 0.01) in male hypertensives. HTN was more prevalent in anemics with high TC than normal TC (38.23% vs 11.17%, P < 0.001) and in non-anemics with high TG than normal TG (56.31% vs 21.22%, P < 0.001). Furthermore, non-anemics with high TG/HDL had the highest risk for HTN (RR = 1.20, 95% CI = 1.1551-1.2473, P < 0.0001). Elevated TC (P = 0.0142), TG (P < 0.0001), TC/HDL (P < 0.0001), LDL/HDL (P < 0.0001), and TG/HDL (P < 0.0001), and low HDL (P < 0.0001) were risk factors for HTN as shown by ORs. In anemics, high TC/HDL, LDL/HDL, and TG/HDL were not. Importantly, only TG and TG/HDL had a discriminating capacity for HTN. Conclusion: The anemic state of hypertensive Saudi patients influences dyslipidemia which warrants further investigation.

Isolated and Combined Effect of Age and Gender on Neutrophil-Lymphocyte Ratio in the Hyperglycemic Saudi Population.

Inflammation is pivotal to the pathogenesis of diabetes mellitus (DM), but pathological alterations of the neutrophil−lymphocyte ratio (NLR), an emerging inflammatory index in DM management, remains understudied. The aim of this study is to examine the relationship between NLR and glycemic control in the Saudi population. Gender, age, WBC count, and fasting blood glucose (FBG) were obtained from Al-Borg Medical Laboratories for 14,205 subjects. Means, prevalence, risk measures, and the diagnostic accuracy of elevated NLR and hyperglycemia (HG) were evaluated. Subjects with elevated NLR (>3) had significantly higher FBG (105.10 ± 0.33 vs. 114.0 ± 2.81) and NLR was significantly elevated in impaired fasting glycemia (IFG; 1.21 ± 0.01 vs. 1.25 ± 0.01) and HG (1.21 ± 0.01 vs. 1.39 ± 0.02). Elevations of NLR in HG but not in IFG persisted across all age groups except young males and elderly females. The prevalence of elevated NLR in hyperglycemic subjects was 4.12% compared to 2.16% in subjects with normal FBG. HG was more prevalent in subjects with elevated NLR (17.33% vs. 12.46%) who had a relative risk (RR) of 1.68 (95% CI = 1.38−2.06, p < 0.0001) and an odds ratio (OR) of 1.94 (95% CI = 1.48−2.56, p < 0.0001) to be hyperglycemic. Nevertheless, NLR failed to discriminate individuals with normal FBG from those with HG based on ROC curve analysis. Pathological fluctuations in NLR may serve as supportive evidence in DM management.

Smart Oral pH-Responsive Dual Layer Nano-Hydrogel for Dissolution Enhancement and Targeted Delivery of Naringenin Using Protein-Polysaccharides Complexation Against Colorectal Cancer.

Naringenin (NAR) is a natural anticancer, but it has not been developed for clinical use despite its therapeutic potential due to its low water solubility, low membrane permeability, first-pass metabolism, and low bioavailability. To overcome these problems, the optimization and preparation of NAR-Soy protein complex (NAR-Sp) led to the optimum ratio of their interaction using Fourier Transform-Infrared spectroscopy (FT-IR) as the first level and layer of the formulation. The second layer of the formulation was to incorporate the NAR-Sp complex in aqueous-based gel-forming. The most optimum nanosuspension was determined using the gel sedimentation, sustained-release, pH-selective and targeted system. The most optimum components combinations and complex were characterized using different characterization tools, such as, the particle size analysis, SEM, TEM, PXRD and FT-IR. In addition, the optimum nanosuspension was characterized for its nanoparticle sensitivity against colorectal cancer cells using MTT assay in comparison to the untreated, naringenin, and blank groups. The complex enhanced the NAR's dissolution. The complex incorporation in the optimum nano-encapsulating system was characterized by the sustained-release and pH-selective behaviors to target the NAR release at the site of action or absorption. Interestingly, the optimum nano-encapsulating system was showing better colorectal cytotoxicity results in comparison to the other groups.

Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds.

Diabetic hyperglycemia delays wound healing, leading to serious consequences. Topical antibiotics can reduce the risk of a wound infection during healing; nevertheless, the microbial fight against antibiotics brings about public health challenges. Anti-microbial peptides (AMPs) belong to a novel class of drug that is used to prevent and treat systemic and topical infections. The aim of the current work was to achieve better wound healing in diabetic rats by conjugating the anti-microbial peptide "apamin" (APA) with the broad-spectrum antibiotic "ceftriaxone" (CTX) to form a nanocomplex. The CTX-APA nanoconjugate formulation was optimized using a Box-Behnken design. The optimized CTX-APA nanoconjugate formulation was evaluated for its size and zeta potential, and was then examined using transmission electron microscopy (TEM). The CTX-APA nanoconjugate was loaded onto a hydroxypropyl methylcellulose (2% w/v)-based hydrogel. It was observed that the application of the CTX-APA nanocomplex on the wounded skin of diabetic rats accelerated the regeneration of the epithelium, granulation tissue formation, epidermal proliferation, and keratinization. The nanocomplex was capable of significantly reducing the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), while increasing the expression of transforming growth factor beta-1 (TGF-ß1) as well as the angiogenic markers: hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Conclusively, the application of an ion-paired CTX-APA nanocomplex enhances wound healing in diabetic rats.

Association between serum uric acid with diabetes and other biochemical markers.

Objective: This study aimed to decipher the association between serum uric acid (UA) and glycated hemoglobin (HbA1c) in the population from the southern region of Saudi Arabia. Method: In this retrospective cross-sectional investigation, clinical data obtained from the different commercial laboratories in the Asir region of Saudi Arabia were screened over 2 years. Data were analyzed using standard statistical methods. Results: A total of 1984 laboratory investigations with 1215 females (61.2%) and 769 males (38.6%) were included in the data analysis. In our investigation, the prevalence of hyperuricemia in the study population was 53.5% (41.2% females and 12.3% males) and in the diabetic population was 12.7% (9.47% females and 3.23% males), in prediabetics was 12.65% (9.8% females and 2.85% males), respectively. Prediabetic subjects had higher UA levels than people with diabetes or healthy people. Higher UA quartiles were associated with a high level of urea, blood urea nitrogen (BUN) creatinine, HbA1c, fasting blood sugar (FBS), and total cholesterol (TC) (P < 0.05). High UA (OR = 1.33 for diabetes; OR = 2.676 for prediabetes), high BUN (OR = 3.05 for diabetes; OR = 2.293 for prediabetes), high TC (OR = 3.75 for diabetes; OR = 1.098 for prediabetes), and high TG (OR = 2.67 for diabetes; OR = 1.943 for prediabetes) parameters are the most influential risk factor in diabetic and prediabetic patients than the people who have normal UA, BUN, TC, and TG value. Conclusion: High UA levels are significantly associated with prediabetes as defined by HbA1c criteria, indicating that UA has a significant role in the disturbance of glucose metabolism. A significant positive association was observed between dyslipidemia and serum UA in the study population.

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells.

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box-Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC50 of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC50 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κß. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.

Effect of Altitude on Hemoglobin and Red Blood Cell Indices in Adults in Different Regions of Saudi Arabia.

Purpose: Complete blood count (CBC) is a commonly used blood test for health checks. This study was conducted to compare CBC from two different altitudes and from sea-level populations in order to suggest correction factor for altitude-related increment on the hemoglobin and red blood cell indices. Patients and Methods: In this retrospective lab records study, large datasets of CBCs over 5-year period were screened from three different regions of Saudi Arabia, Jeddah (a coastal city), Taif City located at 1879 m above sea level, and Abha City at located 2270 m above sea level. Descriptive analysis and significance testing of the CBC variables at different altitude were compared. Results: A total of 57,059 participants were included for final analysis. Mean hemoglobin (Hb) concentration (g/dL) was 14.81 for men and 13.77 for women at sea level, whereas Hb concentrations were 15.35 and 14.19 for men and women residing at Taif City, respectively, and 15.40 and 14.71 for men and women at Abha City, respectively. Hemoglobin and other red cell indices were significantly different among men and women across different altitude, except for mean corpuscular volume (MCV). The MCV 95th percentile range was lower at sea level and both altitudes as compared to current reference range (76-91 fL vs 81-98 fL). Conclusion: Although altitude-associated increment in Hb concentration was evident in both men and women, it was lower than as suggested by World Health Organization and Centers for Disease and Control. Results of this study can also be used to derive new CBC reference intervals for Saudi residents living at high altitude. A correction factor (ΔHb) of 0.30 g/dL per 1000 m altitude is suggested to be used in adult population living at high altitudes in Saudi Arabia which should help better define anemia and polycythemia at altitude.