Racial disparity in uterine leiomyoma: new insights of genetic and environmental burden in myometrial cells.

Uterine leiomyoma (LM), also known as uterine fibroids, are common gynecological tumors and can reach a prevalence of 70% among women by the age of 50 years. Notably, the LM burden is much higher in Black women with earlier onset, a greater tumor number, size, and severity compared to White women. Published knowledge shows that there are genetic, environmental, and lifestyle-based risk factors associated with racial disparity for LM. Significant strides have been made on genomic, epigenomic, and transcriptomic data levels in Black and White women to elucidate the underlying pathomolecular reasons of racial disparity in LM development. However, racial disparity of LM remains a major area of concern in gynecological research. This review highlights risk factors of LM and their role in different races. Furthermore, we discuss the genetics and uterine myometrial microenvironment in LM development. Comparative findings revealed that a major racial difference in the disease is linked to myometrial oxidative burden and altered ROS pathways which is relevant to the oxidized guanine in genomic DNA and MED12 mutations that drive the LM genesis. Considering the burden and morbidity of LM, we anticipate that this review on genetic risk and myometrial microenvironment will strengthen understanding and propel the growth of research to address the racial disparity of LM burden.

Bioactivity-Guided Synthesis: In Silico and In Vitro Studies of ß-Glucosidase Inhibitors to Cope with Hepatic Cytotoxicity.

The major cause of hyperglycemia can generally be attributed to ß-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of ß-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (ß-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with ß-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against ß-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the ß-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug.

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis.

Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase (h-TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h-TNAP, having IC50 values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h-TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure-activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h-TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.

Hydrogen Sulfide Biology and Its Role in Cancer.

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

Pharmacological Inhibition of Endogenous Hydrogen Sulfide Attenuates Breast Cancer Progression.

Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells' viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.

Impact of the factors shaping gut microbiota on obesity.

Obesity is considered as a risk factor for chronic health diseases such as heart diseases, cancer and diabetes 2. Reduced physical activities, lifestyle, poor nutritional diet and genetics are among the risk factors associated with the development of obesity. In recent years, several studies have explored the link between the gut microbiome and the progression of diseases including obesity, with the shift in microbiome abundance and composition being the main focus. The alteration of gut microbiome composition affects both nutrients metabolism and specific gene expressions, thereby disturbing body physiology. Specifically, the abundance of fibre-metabolizing microbes is associated with weight loss and that of protein and fat-metabolizing bacteria with weight gain. Various internal and external factors such as genetics, maternal obesity, mode of delivery, breastfeeding, nutrition, antibiotic use and the chemical compounds present in the environment are known to interfere with the richness of the gut microbiota (GM), thus influencing weight gain/loss and ultimately the development of obesity. However, the effectiveness of each factor in potentiating the shift in microbes' abundance to result in significant changes that can lead to obesity is not yet clear. In this review, we will highlight the factors involved in shaping GM, their influence on obesity and possible interventions. Understanding the influence of these factors on the diversity of the GM and how to improve their effectiveness on disease conditions could be keys in the treatment of metabolic diseases.

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases.

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

Synthesis, evaluation of thymidine phosphorylase and angiogenic inhibitory potential of ciprofloxacin analogues: Repositioning of ciprofloxacin from antibiotic to future anticancer drugs.

Over expression of thymidine phosphorylase (TP) in various human tumors compared to normal healthy tissue is associated with progression of cancer and proliferation. The 2-deoxy-d-ribose is the final product of thymidine phosphorylase (TP) catalyzed reaction. Both TP and 2-deoxy-d-ribose are known to promote unwanted angiogenesis in cancerous cells. Discovery of potent inhibitors of thymidine phosphorylase (TP) can offer appropriate approach in cancer treatment. A series of ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 has been synthesized and characterized using spectroscopic techniques. Afterwards, inhibitory potential of synthesized ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 against thymidine phosphorylase enzyme was assessed. Out of these twelve analogs of ciprofloxacin nine analogues 3a-3c, 4a-4c, 5a-5b and 6 showed good inhibitory activity against thymidine phosphorylase. Inhibitory activity as presented by their IC50 values was found in the range of 39.71 ± 1.13 to 161.89 ± 0.95 µM. The 7-deazaxanthine was used as a standard inhibitor with IC50 = 37.82 ± 0.93 µM. Furthermore, the chick chorionic allantoic membrane (CAM) assay was used to investigate anti-angiogenic activity of the most active ciprofloxacin-based inhibitor 3b. To enlighten the important binding interactions of ciprofloxacin derivatives with target enzyme, the structure activity relationship and molecular docking studies of chosen ciprofloxacin analogues was discussed. Docking studies revealed key π-π stacking, π-cation and hydrogen bonding interactions of ciprofloxacin analogues with active site residues of thymidine phosphorylase enzyme.

Effect of Ramadan fasting on glucose level, lipid profile, HbA1c and uric acid among medical students in Karachi, Pakistan.

To assess the effect of Ramadan fasting on blood pressure, fasting glucose, lipid profile, uric acid, HbA1c, body mass index, body adiposity index and visceral adiposity index among fasting medical students, 35 students were recorded before, during and after Ramadan (August) 2011, for their blood pressure, anthropometric measurements, questionnaire response and blood sample. A blood sample was taken at each visit for glucose, lipid profile and HbA1c. Total physical activity, weight-to-height ratio, body adiposity index and visceral adiposity index were calculated for insulin sensitivity. Changes in anthropometric measurements were not statistically significant. However, physical activities increased significantly after Ramadan. Changes in blood pressure, fasting blood sugar, total cholesterol, HbA1c, uric acid and triglyceride were not statistically significant. Mean high density lipoprotein decreased significantly in Ramadan, while low density lipoprotein increased significantly.

Clinical spectrum of Posterior Reversible Encephalopathy Syndrome (PRES) in patients with eclampsia.

OBJECTIVE: To identify the prevalence, demographic details and clinical features of PRES in women suffering from eclampsia. METHODS: Women admitted in the labor room suite with diagnosis of eclampsia were studied. The study period was from October 15. 2011 to March 15. 2012, in the department of obstetrics & gynecology unit 3, Civil hospital Karachi. Of all patients with diagnosis of eclampsia, 22 underwent neuro imaging by computerized tomography. Demographic details, clinical findings and maternal and perinatal outcome were entered on a predesigned Performa. RESULTS: Thirty four women were identified, with eclampsia. Neuro imaging was done in 22 women. Posterior reversible encephalopathy syndrome was recognized in 9 (22) patients. The mean systolic blood pressure was 161(±11) mm Hg, and mean diastolic blood pressure was 111(±10) mm Hg. Mean number of fits were three, and the mean gestational age of patients were 35 weeks. Gestational age was found significantly associated with PRES (p <0.3) Mean leukocyte count in patients with eclampsia was 20,083±16,165/cu mm. CONCLUSION: Our study shows presence of Posterior reversible encephalopathy syndrome (PRES) in women who are identified with eclampsia. There is need for awareness and long term neurological follow up in this group of women.

SEQUEL: Prevalence of dental caries in Saudi Arabia: A systematic review and Meta-analysis.

This meta-analysis investigated the prevalence of dental caries throughout the Kingdom of Saudi Arabia (KSA) between 2011 and 2023 as a follow-up to a previously published review in 2013 by Khan et al. and aimed to provide an update on the current status of caries prevalence in the KSA. A literature search was conducted, and thirty-three articles were included in the final analysis. To determine the prevalence of caries in primary teeth, the 2- to 12-year-old Saudi population was included in the search, and an age range of 6-18 years was used for permanent teeth. The prevalence of caries in the primary and permanent dentition was analyzed separately. As the included studies for the primary and permanent teeth had insignificant heterogeneity, fixed-effect models and forest plots were used to evaluate caries prevalence in both dentitions. In the primary dentition, the mean decayed-missing-filled teeth (dmft) index was 4.14 (95 % confidence interval (CI): 3.11-5.18), with an average prevalence of 75.43 %. For the permanent teeth, the mean DMFT (uppercase used for permanent dentition) was 1.28 (95 % CI: 0.93-1.64), with an average prevalence of 67.7 %. The average dmft/DMFT scores decreased in both primary and permanent teeth compared to the previous meta-analysis by Khan et al., suggesting a beneficial effect of preventative measures on caries prevalence. Continuing these measures is necessary to maintain the downward trend of caries prevalence in the KSA.

Thrombophilia investigation in Pakistani women with recurrent pregnancy loss.

AIM: The aim of the study was to identify thrombophilic defects in women with a history of recurrent miscarriage. METHODS: This was a case-control study in which the cases were women who had undergone spontaneous recurrent pregnancy losses and the controls were women in matched reproductive age groups without any history of miscarriage or pregnancy loss. Both groups of women were identified from our department's high-risk and gynecological outpatient clinics. A total of 52 women with recurrent pregnancy losses and 268 controls were tested for protein C, protein S, factor V Leiden (FVL), antithrombin and anticardiolipin (immunoglobulin M and G) antibodies, and the odds ratio and P-values were calculated. RESULTS: The mean age was 28.0 ± 4.4 years in the cases and 32.0±8.0years in the controls. The mean number of abortions among women with recurrent losses was 3.40±1.23. The mean parity was 1.04±1.23 (range 1-6), and 3.27±2.51 among controls. Among women with recurrent pregnancy loss, 22 (42%) had first trimester losses, 19 (36%) had second trimester losses, and 11 (21%) women had both first and second trimester losses. Protein C deficiency was identified in three out of 52 cases and 18 out of 268 controls (P-value 0.49), protein S deficiency in two cases and 12 controls (P-value 0.35), factor V Leiden mutation in 10 cases and 27 controls (P = 0.059), antithrombin in one case and 41 controls (P=0.009), and anticardiolipin antibodies in one case and nine controls (P = 0.49). CONCLUSION: No significant association between inherited thrombophilia and recurrent pregnancy loss in Pakistani women was found.

MRI features of spinal Fluorosis: Results of an endemic community screening.

OBJECTIVES: Fluorosis is endemic in many parts of the world. However community studies on MRI features of fluorosis are lacking. The aim of this study was to determine MRI features of spinal changes in a community with endemic fluorosis in the Thar Desert Pakistan. METHODOLOGY: Randomly selected adults from the Village Samorindh, district Tharparker, Sindh, Pakistan, with spinal fluorosis diagnosed on plain x-rays and raised serum fluoride levels were studied from June 2008 to January 2009. MRI was carried out on 0.5 T open magnet MRI system. Features of vertebral body, spinal ligaments, intervertebral disc, facet joints, iliac wings and other incidental findings were noted. Sclerosis was defined as low signal intensity on both T1 and T2 weighted images. RESULTS were described as mean and percentage values. RESULTS: All the studied 27 subjects complained of back ache without neurological signs. The average age was 43.33 ± 10.45 years; 21 being male (77.8%). The most frequent findings included generalized vertebral sclerosis (24, 88.8%), ligamentum flavum hypertrophy (23, 85%), anterior (20, 74%) and lateral (17, 62.9%) disc herniation, thickened longitudinal ligaments, and narrowing of spinal foramina. Hemangioma was seen in 04(14.8%). The most commonly involved level was L1-2, L4-5 and lower dorsal spine. CONCLUSION: Vertebral sclerosis, a combination of premature degeneration with anterior disc herniation and an unusually high frequency of vertebral hemangioma formed the spectrum of MRI findings in subjects with spinal fluorosis having back ache but no neurological findings.

Effect of Fipronil Exposure on Hematological Aspects of Rhesus Monkeys (Macaca mulatta): Risk and Toxicity Assessment in Agro-Workers.

Background: Fipronil (FPN) is a broad-spectrum phenylpyrazole insecticide, widely used in agriculture and veterinary medicine. Published research on FPN toxicity has established the fact that its inhalation or dermal exposure may lead to very serious clinical outcomes in non-target animals. In line to its exposure and toxicity related damage, FPN has been investigated in many invertebrates, however, its exposure-related noxiousness is less reported in higher animals. Objective: To assess the FPN-induced effects to agro-workers in the field, in the present study, we used physiological human surrogates, adult rhesus monkeys as models. Method: We exposed well habituated, chair restraint adult rhesus monkeys with a field spray concentration of FPN (0.3 mg/1 mL distilled water) through an inhalation route in the closed system. Animals were divided into control and treatment groups, each containing three animals. Inflammatory and hematological effects were determined by evaluating the kidney and liver biomarker enzymes; serum creatinine and alanine transaminase (ALT), aspartate transaminase (AST) levels respectively. Results: Our findings reveal that FPN treated monkeys show significantly increased levels of ALT (p = 0.000461), AST (p = 0.0681) and creatinine (p = 0.00656) as compared to the control group. Furthermore, significant differences of red blood cells (RBCs) (p = 0.0139) and white blood cells (WBCs) (p = 0.00642) were also observed in the treated and control group monkeys which reflect strong toxic effects on the blood cells. Conclusion: Our findings demonstrate that FPN exposure is very toxic to higher animals and causes severe damage to the liver and kidneys along with other clinical problems. The study highlights the effect and impact of passive inhalation of insecticides in intentionally carefree agro-workers and raises the concern of public awareness toward pesticides use.

Pathophysiological Association of Alzheimer's Disease and Hypertension: A Clinical Concern for Elderly Population.

Alzheimer's disease (AD), the most common cause of dementia and the fifth leading cause of death in the adult population has a complex pathophysiological link with hypertension (HTN). A growing volume of published literature on a parallel elevation of blood pressure (BP), amyloid plaques, and neurofibrillary tangles formation in post-middle of human brain cells has developed new, widely accepting foundations on this association. In particular, HTN in elderly life mediates cerebral blood flow dysfunction, neuronal dysfunction, and significant decline in cognitive impairment, primarily in the late-life populace, governing the onset of AD. Thus, HTN is an established risk factor for AD. Considering the impact of AD, 1.89 million deaths annually, and the failure of palliative therapies to cure AD, the scientific research community is looking to adopt integrated approaches to target early modified risk factors like HTN to reduce AD burden. The current review highlights the significance and impact of HTN-based prevention in lowering the AD burden in the elderly by providing a comprehensive overview of the physiological relationship between AD and HTN with an in-detail explanation of the role and applications of pathological biomarkers in this clinical association. The review will gain worth in presenting new insights and providing inclusive discussion on the correlation between HTN and cognitive impairment. It will increase across a wider scientific audience to expand understanding of this pathophysiological association.

How fear of intimacy affects infertile men's neuropsychological functioning through mental toughness.

Objective: There is a significant need in Pakistan to investigate the psychological effects of infertility on the mental health of infertile men. The current study examined how fear of intimacy affects neuropsychological impairment and evaluated its relationship to other variables including quality of life and mental toughness. Method: An analytical cross-sectional study was carried out on infertile male patients in various healthcare settings in Punjab, Pakistan. The participants were recruited using a non-probability (purposive) sampling strategy. The sample size was 120 infertile. SPSS 26 was used to analyze the data. Results: Fear of intimacy was found significant impact on neuropsychological impairment (r = 0.40; ***p < 0.001), as well as fear of intimacy, significantly associated with emotional problems (r = 0.48; **p < 0.01), learning problems (r = 0.33; **p < 0.01), sensory and motor problem (r = 0.55; **p < 0.01), concentration problem (r = 0.21; **p < 0.01), mental & physical in coordination (r = 0.37; **p < 0.01) and depression (r = 0.22; **p < 0.01). Fear of intimacy has negative impact on QoL (r = -0.25; *p > 0.05). Similarly, neuropsychological impairment was found to be negatively associated with QoL (r = -0.52; **p > 0.01). The relationship between fear of intimacy and neuropsychological impairment was found to be significantly mediated by QoL. Furthermore, the findings revealed that mental toughness significantly moderated the relationship between fear of intimacy and neuropsychological impairment. Conclusion: Overall, infertile men in Pakistan had relatively high levels of fear of intimacy, which largely caused neuropsychological impairment. This study can help neuropsychological researchers, mental health professionals, as well as policymakers in improving clinical mental health practices for infertile patients.

A Water-Soluble Hydrogen Sulfide Donor Suppresses the Growth of Hepatocellular Carcinoma via Inhibiting the AKT/GSK-3ß/ß-Catenin and TGF-ß/Smad2/3 Signaling Pathways.

Hepatocellular carcinoma (HCC) is a disease with high morbidity, high mortality, and low cure rate. Hyaluronic acid (HA) is widely adopted in tissue engineering and drug delivery. 5-(4-Hydroxyphenyl)-3H-1, 2-dithiol-3-thione (ADT-OH) is one of commonly used H2S donors. In our previous study, HA-ADT was designed and synthesized via coupling of HA and ADT-OH. In this study, compared with sodium hydrosulfide (NaHS, a fast H2S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H2S-releasing donor), HA-ADT showed stronger inhibitory effect on the proliferation, migration, invasion, and cell cycle of human HCC cells. HA-ADT promoted apoptosis by suppressing the expressions of phospho (p)-protein kinase B (PKB/AKT), p-glycogen synthase kinase-3ß (GSK-3ß), p-ß-catenin, and also inhibited autophagy via the downregulation of the protein levels of p-Smad2, p-Smad3, and transforming growth factor-ß (TGF-ß) in human HCC cells. Moreover, HA-ADT inhibited HCC xenograft tumor growth more effectively than both NaHS and GYY4137. Therefore, HA-ADT can suppress the growth of HCC cells by blocking the AKT/GSK-3ß/ß-catenin and TGF-ß/Smad2/3 signaling pathways. HA-ADT and its derivatives may be developed as promising antitumor drugs.

Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration.

Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer's disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.

Complete monosaccharide analysis by high-performance anion-exchange chromatography with pulsed amperometric detection.

Monosaccharide analysis is a critical way to profile the composition of complex carbohydrates. Methods to analyze neutral and amino sugars have been established for a long time, but methods for acidic sugars are rare. The acidic sugars, including uronic acids and sialic acids, are also important components in some complex carbohydrates. In this report, a high-performance anion-exchange chromatography method with pulsed amperometric detection was initially developed to analyze acidic sugars including different uronic acids and sialic acids. Subsequently, a method to profile complete monosaccharides, including most neutral, amino, and acidic sugars, was developed. This method has a limit of quantitation of ~12.5 × 10(-3) nmol for each sugar as well as good linearity over a wide range. This is a convenient procedure because it avoids additional derivatization of monosaccharides and has a broad application to a wide range of complex carbohydrates. The monosaccharide compositions of a variety of complex carbohydrates such as different glycosaminoglycans, alginate, fucoidan, and glycans were profiled by this comprehensive method. In addition, the hydrolysis patterns of these complex carbohydrates are discussed.

Prevalence and factors related to dental caries among pre-school children of Saddar town, Karachi, Pakistan: a cross-sectional study.

BACKGROUND: Dental caries is highly prevalent and a significant public health problem among children throughout the world. Epidemiological data regarding prevalence of dental caries amongst Pakistani pre-school children is very limited. The objective of this study is to determine the frequency of dental caries among pre-school children of Saddar Town, Karachi, Pakistan and the factors related to caries. METHODS: A cross-sectional study of 1000 preschool children was conducted in Saddar town, Karachi. Two-stage cluster sampling was used to select the sample. At first stage, eight clusters were selected randomly from total 11 clusters. In second stage, from the eight selected clusters, preschools were identified and children between 3- to 6-years age group were assessed for dental caries. RESULTS: Caries prevalence was 51% with a mean dmft score being 2.08 (±2.97) of which decayed teeth constituted 1.95. The mean dmft of males was 2.3 (±3.08) and of females was 1.90 (±2.90). The mean dmft of 3, 4, 5 and 6-year olds was 1.65, 2.11, 2.16 and 3.11 respectively. A significant association was found between dental caries and following variables: age group of 4-years (p-value < 0.029, RR = 1.248, 95% Bias corrected CI 0.029-0.437) and 5-years (p-value < 0.009, RR = 1.545, 95% Bias corrected CI 0.047-0.739), presence of dental plaque (p-value < 0.003, RR = 0.744, 95% Bias corrected CI (-0.433)-(-0.169)), poor oral hygiene (p-value < 0.000, RR = 0.661, 95% Bias corrected CI (-0.532)-(-0.284)), as well as consumption of non-sweetened milk (p-value < 0.049, RR = 1.232, 95% Bias corrected CI 0.061-0.367). CONCLUSION: Half of the preschoolers had dental caries coupled with a high prevalence of unmet dental treatment needs. Association between caries experience and age of child, consumption of non-sweetened milk, dental plaque and poor oral hygiene had been established.