Awareness of Stem Cell Therapy for Diabetes Among Type II Diabetic Patients in Makkah: A Cross-Sectional Study.

Background Diabetes mellitus is a chronic disease that affects millions of people worldwide. Several studies have suggested using stem cells for diabetes treatment. However, there is a lack of research assessing the population's awareness of stem cells. This study aimed to evaluate the level of awareness regarding the use of stem cell therapy for type 2 diabetes mellitus (T2DM). Methodology This study was conducted from December 2021 to April 2022 through an online survey that was distributed electronically via social media platforms. T2DM patients or their care providers who lived in Makkah were included. Patients aged less than 18 years and those with mental disabilities were excluded. Results Of the 316 participants included in the study, 56% were males, 33% had an age range of 46-55 years, and 76% were married. T2DM patients and their caregivers had a moderate level of awareness about stem cell therapy, with caregivers having higher awareness than diabetic patients. A non-significant relationship was found between educational level, income, diabetes control, time of diagnosis, and patients' awareness. However, regarding the decision of treatment, participants aged less than 35 years were highly likely to decide to undergo stem cell treatment compared to other age groups. Conclusions There is a moderate level of awareness about stem cell therapy as a treatment option for T2DM among T2DM patients and caregivers in Makkah. Hence, there is a need to raise awareness by using online and in-person well-organized education programs in Makkah.

The Association between Colorectal Cancer and Colonoscopic Conditions in Saudi Patients: A 10-Year Cross-Sectional-Retrospective Study.

Background: In Saudi Arabia, colorectal cancer (CRC) is the most common cancer in males and the third most common cancer in females. The current gold standard for colorectal cancer diagnosis is colonoscopy. Several concerns regarding the balance of ordering colonoscopy procedures for patients presenting with signs and symptoms. There are also several concerns regarding over-ordering the procedure when unnecessary. The current study aimed to evaluate the association between colorectal cancer and colonoscopic conditions in Saudi patients. Methods: A 10-year cross-sectional study was conducted at Alnoor Specialty Hospital, Makkah, over the last ten years. Colonoscopy reports of patients were evaluated to identify the colonoscopy manifestations associated with mass, polyps, and bleeding. Results: The current study evaluated 2158 cases admitted to the hospital for colonoscopic diagnosis. Results indicated that most of the patients were males (55.4%). Additionally, results showed a significant statistical association between tumor and bleeding, polyp, and hemorrhage. Moreover, it highlighted the association between polyps and bleeding, inflammation, and diverticulosis. Conclusion: CRC screening in Saudi Arabia is comprehensive; however, there are a few areas for improvement, including standardization of colorectal cancer pathology reporting to improve the health system's quality. Also, the current study identified conditions that are significantly associated with reported colon polyps and tumors, which could aid in stratifying patients selected for screening via colonoscopy.

Complete chloroplast genome of the desert date (Balanites aegyptiaca (L.) Del. comparative analysis, and phylogenetic relationships among the members of Zygophyllaceae.

BACKGROUND: Balanites aegyptiaca (L.) Delile, commonly known as desert date, is a thorny evergreen tree belonging to the family Zygophyllaceae and subfamily Tribuloideae that is widespread in arid and semiarid regions. This plant is an important source of food and medicines and plays an important role in conservation strategies for restoring degraded desert ecosystems. RESULTS: In the present study, we sequenced the complete plastome of B. aegyptiaca. The chloroplast genome was 155,800 bp, with a typical four-region structure: a large single copy (LSC) region of 86,562 bp, a small single copy (SSC) region of 18,102 bp, and inverted repeat regions (IRa and IRb) of 25,568 bp each. The GC content was 35.5%. The chloroplast genome of B. aegyptiaca contains 107 genes, 75 of which coding proteins, 28 coding tRNA, and 4 coding rRNA. We did not observe a large loss in plastid genes or a reduction in the genome size in B. aegyptiaca, as found previously in some species belonging to the family Zygophyllaceae. However, we noticed a divergence in the location of certain genes at the IR-LSC and IR-SSC boundaries and loss of ndh genes relative to other species. Furthermore, the phylogenetic tree constructed from the complete chloroplast genome data broadly supported the taxonomic classification of B. aegyptiaca as belonging to the Zygophyllaceae family. The plastome of B. aegyptiaca was found to be rich in single sequence repeats (SSRs), with a total of 240 SSRs. CONCLUSIONS: The genomic data available from this study could be useful for developing molecular markers to evaluate population structure, investigate genetic variation, and improve production programs for B. aegyptiaca. Furthermore, the current data will support future investigation of the evolution of the family Zygophyllaceae.

Exogenous administration of unacylated ghrelin attenuates hepatic steatosis in high-fat diet-fed rats by modulating glucose homeostasis, lipogenesis, oxidative stress, and endoplasmic reticulum stress.

Low levels of unacylated ghrelin (UAG) and a higher ratio of acylated ghrelin (AG)/UAG in obesity are associated with non-alcoholic fatty liver disease (NAFLD). This study tested the potential protective effect of increased circulatory levels of UAG by exogenous UAG administration on hepatic steatosis in high-fat diet (HFD)-fed rats and investigated some possible mechanisms. Rats were divided (n = 6/group) as low fat diet (LFD), LFD + UAG (200 mg/kg), HFD, HFD + UAG (50, 100, or 200 mg/kg). Treatments were given for 8 weeks. Increasing the dose of UAG increased circulatory levels of UAG and normalized the ratio of AG/UAG at the dose of 200 mg/kg. With no change in insulin levels, and in a dose-dependent manner, treatment with UAG to HFD rats attenuated the gain in food intake, body weights, and liver weights, lowered fasting glucose levels, prevented hepatic cytoplasmic vacuolization, and reduced serum and hepatic levels of cholesterol, triglycerides, and free fatty acids. They also progressively reduced levels of reactive oxygen species, lipid peroxides, tumor necrosis factor-α, and interleukin-6, as well as mRNA levels of Bax and caspase-3 but increased levels of glutathione and superoxide dismutase and mRNA levels of Bcl2. In concomitant, UAG, in a dose-response manner, significantly reduced hepatic mRNA levels of SREBP1, SREBP2, ATF-6, IRE-1, and eIF-2α but increased those of PPARα. In conclusion, reducing the circulatory ratio of AG/UAG ratio by exogenous administration of UAG attenuates HFD-induced hepatic steatosis by suppressing lipogenesis, stimulating FAs oxidation, preventing oxidative stress, inflammation, ER stress, and apoptosis.

Leucine-rich repeat-containing G protein-coupled receptor 5 marks different cancer stem cell compartments in human Caco-2 and LoVo colon cancer lines.

BACKGROUND: Colon cancer cell lines are widely used for research and for the screening of drugs that specifically target the stem cell compartment of colon cancers. It was reported that colon cancer carcinoma specimens contain a subset of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)-expressing stem cells, these so-called "tumour-initiating" cells, reminiscent in their properties of the normal intestinal stem cells (ISCs), may explain the apparent heterogeneity of colon cancer cell lines. Also, colon cancer is initiated by aberrant Wnt signaling in ISCs known to express high levels of LGR5. Furthermore, in vivo reports demonstrate the clonal expansion of intestinal adenomas from a single LGR5-expressing cell. AIM: To investigate whether colon cancer cell lines contain cancer stem cells and to characterize these putative cancer stem cells. METHODS: A portable fluorescent reporter construct based on a conserved fragment of the LGR5 promoter was used to isolate the cell compartments expressing different levels of LGR5 in two widely used colon cancer cell lines (Caco-2 and LoVo). These cells were then characterized according to their proliferation capacity, gene expression signatures of ISC markers, and their tumorigenic properties in vivo and in vitro. RESULTS: The data revealed that the LGR5 reporter can be used to identify and isolate a classical intestinal crypt stem cell-like population from the Caco-2, but not from the LoVo, cell lines, in which the cancer stem cell population is more akin to B lymphoma Moloney murine leukemia virus insertion region 1 homolog (+4 crypt) stem cells. This sub-population within Caco-2 cells exhibits an intestinal cancer stem cell gene expression signature and can both self-renew and generate differentiated LGR5 negative progeny. Our data also show that cells expressing high levels of LGR5/enhanced yellow fluorescent protein (EYFP) from this cell line exhibit tumorigenic-like properties in vivo and in vitro. In contrast, cell compartments of LoVo that are expressing high levels of LGR5/EYFP did not show these stem cell-like properties. Thus, cells that exhibit high levels of LGR5/EYFP expression represent the cancer stem cell compartment of Caco-2 colon cancer cells, but not LoVo cells. CONCLUSION: Our findings highlight the presence of a spectrum of different ISC-like compartments in different colon cancer cell lines. Their existence is an important consideration for their screening applications and should be taken into account when interpreting drug screening data. We have generated a portable LGR5-reporter that serves as a valuable tool for the identification and isolation of different colon cancer stem cell populations in colon cancer lines.

Taxonomic revision of Ceropegia sect. Huernia (Asclepiadoideae, Apocynaceae) in Saudi Arabia with three new combinations.

This study provides a taxonomic revision for Ceropegia sect. Huernia in the flora of Saudi Arabia. Forty-six quantitative and qualitative morphological characters were analysed using principal component analysis (PCA), principal coordinates analysis (PCoA) and the unweighted pairs group using mean average (UPGMA) to separate and help delimit taxa. We propose to reduce the number of species reported in Saudi Arabia from 11 to four: C. khalidbinsultanii comb. nov., C. laevis, C. lodarensis and C. macrocarpa. This study also suggested reducing two names to varietal level under C. lodarensis (var. foetidacomb. nov. and var. rubrostictacomb. nov.). A key to the species, detailed morphological descriptions, illustrations, distribution maps, ecology, etymology and preliminary conservation assessments are provided that follow IUCN criteria.

Exendin-4 Protects Against Myocardial Ischemia-Reperfusion Injury by Upregulation of SIRT1 and SIRT3 and Activation of AMPK.

This study evaluated if the cardioprotective effect of Exendin-4 against ischemia/reperfusion (I/R) injury in male rats involves modulation of AMPK and sirtuins. Adult male rats were divided into sham, sham + Exendin-4, I/R, I/R + Exendin-4, and I/R + Exendin-4 + EX-527, a sirt1 inhibitor. Exendin-4 reduced infarct size and preserved the function and structure of the left ventricles (LV) of I/R rats. It also inhibited oxidative stress and apoptosis and upregulated MnSOD and Bcl-2 in their infarcted myocardium. With no effect on SIRTs 2/6/7, Exendin-4 activated and upregulated mRNA and protein levels of SIRT1, increased levels of SIRT3 protein, activated AMPK, and reduced the acetylation of p53 and PGC-1α as well as the phosphorylation of FOXO-1. EX-527 completely abolished all beneficial effects of Exendin-4 in I/R-induced rats. In conclusion, Exendin-4 cardioprotective effect against I/R involves activation of SIRT1 and SIRT3. Graphical Abstract Exendin-4 could scavenge free radical directly, upregulate p53, and through upregulation of SIRT1 and stimulating SIRT1 nuclear accumulation. In addition, Exendin-4 also upregulates SIRT3 which plays an essential role in the upregulation of antioxidants, inhibition of reactive oxygen species (ROS) generation, and prevention of mitochondria damage. Accordingly, SIRT1 induces the deacetylation of PGC-1α and p53 and is able to bind p-FOXO-1. This results in inhibition of cardiomyocyte apoptosis through increasing Bcl-2 levels, activity, and levels of MnSOD; decreasing expression of Bax; decreasing cytochrome C release; and improving mitochondria biogenesis through upregulation of Mfn-2.

Illumination Adaptation in a Multi-Wavelength Opto-Electronic Patch Sensor.

In capturing high-quality photoplethysmographic signals, it is crucial to ensure that appropriate illumination intensities are used. The purpose of the study was to deliver controlled illumination intensities for a multi-wavelength opto-electronic patch sensor that has four separate arrays each consisting of four light-emitting diodes (LEDs), the wavelength of the light generated by each array being different. The study achieved the following: (1) a linear constant current source LED driver incorporating series negative feedback using an integrated operational amplifier circuit; (2) the fitting of a linear regression equation to provide rapid determination of the LEDs driver voltage; and (3) an algorithm for the automatic adjustment of the output voltage to ensure suitable LED illumination. The data from a single centrally-located photo detector, which is capable of capturing all four channels of back-light in a time-multiplexed manner, were used to monitor heart rate and blood oxygen saturation. This paper provides circuitry for driving the LEDs and describes an adaptive algorithm implemented on a microcontroller unit that monitors the quality of the photo detector signals received in order to control each of the individual currents being supplied to the LED arrays. The study demonstrated that the operation of the new circuitry in its ability to adapt LED illumination to the strength of the signal received and the performance of the adaptive system was compared with that of a non-adaptive approach.

Exendin-4 Ameliorates Cardiac Remodeling in Experimentally Induced Myocardial Infarction in Rats by Inhibiting PARP1/NF-κB Axis in A SIRT1-Dependent Mechanism.

Sirt1 is a potent inhibitor of both poly(ADP-ribose) polymerases1 (PARP1) and NF-kB. This study investigated the cardioprotective effect of exendin-4 on cardiac function and remodeling in rats after an expreimentally-induced myocardial infarction (MI) and explored if this protection involves SIRT1/PARP1 axis. Rats were divided into five groups (n = 10/each): sham, sham + exendin-4 (25 nmol/kg/day i.p.), MI (induced by LAD occlusion), MI + exendin-4, and sham + exendin-4 + EX527 (5 mg/2×/week) (a SIRT1 inhibitor). All treatments were given for 6 weeks post the induction of MI. In sham-operated and MI-induced rats, exendin-4 significantly upregulated Bcl-2 levels, enhanced activity, mRNA, and levels of SIRT1, inhibited activity, mRNA, and levels of PARP1, and reduced ROS generation and PARP1 acetylation. In MI-treated rats, these effects were associated with improved cardiac architectures and LV function, reduced collagen deposition, and reduced mRNA and total levels of TNF-α and IL-6, as well as, the activation of NF-κB p65. In addition, exendin-4 inhibited the interaction of PARP1 with p300, TGF-ß1, Smad3, and NF-κB p65 and signficantly reduced mRNA and protein levels of collagen I/III and protein levels of MMP2/9. In conclusion, exendin-4 is a potent cardioprotective agent that prevents post-MI inflammation and cardiac remodeling by activating SIRT1-induced inhibition of PARP1.

The apoptotic effect of resveratrol in ovarian cancer cells is associated with downregulation of galectin-3 and stimulating miR-424-3p transcription.

This study investigated if the well-reported anti-tumor effects of resveratrol (RES) is mediated by modulation levels of galectin-3 (GAL-3), an anti-apoptotic lectin that is highly overexpressed in ovarian cancer cells. SKOV3 and OVCAR-3 OC cells were untreated or incubated with DMOS or increasing concentrations of RES (25, 50, 100 µM) for 72 hr. RES, in a dose-dependent manner and in both cell lines, induced cell death and inhibited cell migration and invasion It also downregulated Bcl-2 levels, increased cleaved caspase-3, and GAL-3 protein (but not mRNA) levels, suggesting increased breakdown. These effects were associated with reduced levels of p-NF-κB P65, p-IKKα/ß, and p-Akt, major targets of Gal-3. Further investigation showed that RES enhanced levels of miR-424-3p which is able to degrade GAL-3. Conclusion: Findings of this study suggest that RES induced apoptosis in cancerous cells is associated with increased levels of miR-424-3p and reduced levels of GAL-3. PRACTICAL APPLICATIONS: This study highlights a possible mechanism by which RES could enhance cell death in OC cells and enhances their sensitivity to cisplatin. RES apoptotic effect and enhancement of OC cells to chemotherapy were associated with decreased abundance of GAL-3, a common cell survival molecule that promotes tumorigenesis and increased transcription of miR-424-3p that has the ability to degrade cellular GAL-3. These findings add a possible new mechanism by which RES acts and opens a window for further research to understand its mechanism of action.

Oxygen Saturation Measurements from Green and Orange Illuminations of Multi-Wavelength Optoelectronic Patch Sensors.

Photoplethysmography (PPG) based pulse oximetry devices normally use red and infrared illuminations to obtain oxygen saturation (SpO2) readings. In addition, the presence of motion artefacts severely restricts the utility of pulse oximetry physiological measurements. In the current study, a combination of green and orange illuminations from a multi-wavelength optoelectronic patch sensor (mOEPS) was investigated in order to improve robustness to subjects' movements in the extraction of SpO2 measurement. The experimental protocol with 31 healthy subjects was divided into two sub-protocols, and was designed to determine SpO2 measurement. The datasets for the first sub-protocol were collected from 15 subjects at rest, with the subjects free to move their hands. The datasets for the second sub-protocol with 16 subjects were collected during cycling and walking exercises. The results showed good agreement with SpO2 measurements (r = 0.98) in both sub-protocols. The outcomes promise a robust and cost-effective approach of physiological monitoring with the prospect of providing health monitoring that does not restrict user physical movements.

A Multi-Wavelength Opto-Electronic Patch Sensor to Effectively Detect Physiological Changes against Human Skin Types.

Different skin pigments among various ethnic group people have an impact on spectrometric illumination on skin surface. To effectively capture photoplethysmographic (PPG) signals, a multi-wavelength opto-electronic patch sensor (OEPS) together with a schematic architecture of electronics were developed to overcome the drawback of present PPG sensor. To perform a better in vivo physiological measurement against skin pigments, optimal illuminations in OEPS, whose wavelength is compatible with a specific skin type, were optimized to capture a reliable physiological sign of heart rate (HR). A protocol was designed to investigate an impact of five skin types in compliance with Von Luschan's chromatic scale. Thirty-three healthy male subjects between the ages of 18 and 41 were involved in the protocol implemented by means of the OEPS system. The results show that there is no significant difference (p: 0.09, F = 3.0) in five group tests with the skin types across various activities throughout a series of consistent measurements. The outcome of the present study demonstrates that the OEPS, with its multi-wavelength illumination characteristics, could open a path in multiple applications of different ethnic groups with cost-effective health monitoring.

Transgenic human ES and iPS reporter cell lines for identification and selection of pluripotent stem cells in vitro.

Optimization of pluripotent stem cell expansion and differentiation is facilitated by biological tools that permit non-invasive and dynamic monitoring of pluripotency, and the ability to select for an undifferentiated input cell population. Here we report on the generation and characterisation of clonal human embryonic stem (HES3, H9) and human induced pluripotent stem cell lines (UQEW01i-epifibC11) that have been stably modified with an artificial EOS(C3+) promoter driving expression of EGFP and puromycin resistance-conferring proteins. We show that EGFP expression faithfully reports on the pluripotency status of the cells in these lines and that antibiotic selection allows for an efficient elimination of differentiated cells from the cultures. We demonstrate that the extinction of the expression of the pluripotency reporter during differentiation closely correlates with the decrease in expression of conventional pluripotency markers, such as OCT4 (POU5F1), TRA-1-60 and SSEA4 when screening across conditions with various levels of pluripotency-maintaining or differentiation-inducing signals. We further illustrate the utility of these lines for real-time monitoring of pluripotency in embryoid bodies and microfluidic bioreactors.