In vitro degradation, swelling, and bioactivity performances of in situ forming injectable chitosan-matrixed hydrogels for bone regeneration and drug delivery.

Injectable, tissue mimetic, bioactive, and biodegradable hydrogels offer less invasive regeneration and repair of tissues. The monitoring swelling and in vitro degradation capacities of hydrogels are highly important for drug delivery and tissue regeneration processes. Bioactivity of bone tissue engineered constructs in terms of mineralized apatite formation capacity is also pivotal. We have previously reported in situ forming chitosan-based injectable hydrogels integrated with hydroxyapatite and heparin for bone regeneration, promoting angiogenesis. These hydrogels were functionalized by glycerol and pH to improve their mechano-structural properties. In the present study, functionalized hybrid hydrogels were investigated for their swelling, in vitro degradation, and bioactivity performances. Hydrogels have degraded gradually in phosphate-buffered saline (PBS) with and without lysozyme enzyme. The percentage weight loss of hydrogels and their morphological and chemical properties, and pH of media were analyzed. The swelling ratio of hydrogels (55%-68%(wt), 6 h of equilibrium) indicated a high degree of cross-linking, can be suitable for controlled drug release. Hydrogels have gradually degraded reaching to 60%-70% (wt%) in 42 days in the presence and absence of lysozyme, respectively. Simulated body fluid (SBF)-treated hydrogels containing hydroxyapatite-induced needle-like carbonated-apatite mineralization was further enhanced by heparin content significantly.

Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants.

This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between LOX gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while LOX gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (p < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (p < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, LOX gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30-24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.

Photophysical and biological aspects of α, ß-unsaturated ketones: Experimental and in silico approach.

In this work, four fluorinated α, ß-unsaturated ketones named as 3-(3-bromophenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (1), 3-(4-methoxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (2), 3-(3-bromo-5-chloro-2-hydroxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (3) and 3-(2-hydroxy-5-methylphenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (4) were synthesized by Claisen-Schmidt reaction. The synthesized molecules were then characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), 1 H-NMR, 13 C-NMR, and mass spectrometry. The antioxidant potential, Urease inhibition, and interaction of compounds 1-4 with Salmon sperm DNA were experimentally explored and supported by molecular docking studies. The synthesized compounds strongly interact with SS-DNA through intercalative mode. It was noticed that compound 1 served as potent Urease inhibitor while compound 4 as better antioxidant among synthesized compounds. Moreover, frontier molecular orbitals, nonlinear optical (NLO) properties, natural bond orbitals, molecular electrostatic potential, natural population analysis, and photophysical properties of synthesized compounds were accomplished through density functional theory and time-dependent density functional theory. The band gap of all the compounds have been worked out using Taucs method. In addition to that, a precise comparative account of UV and IR data obtained from theoretical and experimental findings showed good agreement between theoretical and experimental data. The findings of our studies reflected that compounds 1-4 possess better NLO properties than Urea standard and the band gap data also reflected their prospective use towards optoelectronic materials. The better NLO behavior of compounds was attributed to the noncentrosymmetric structure of synthesized compounds.

Association of MSX1 Gene Variants with Nonsyndromic Cleft Lip and/or Palate in the Pakistani Population.

OBJECTIVES: This study investigated the association of MSX1 gene variants rs3821949 and rs12532 with nonsyndromic cleft lip and/or palate (NSCL/P) in the Pakistani population. DESIGN: Comparative cross-sectional study.Setting: Multicenter of CL/P malformation.Patients/Participants: Unrelated Non-Syndromic cleft Lip/Palate patients and healthy controls were enrolled. METHODS: One hundred (n = 100) subjects with NSCL/P and n = 50 unrelated healthy controls were enrolled in a multicenter comparative cross-sectional study. A tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to analyze MSXI gene single nucleotide variants (SNVs). RESULTS: Among 100 NSCL/P subjects, the majority were males (56%; male: female = 1.27: 1). Most of the cases (74%) had cleft lip and palate (CLP) compared to isolated clefts. Genotyping of MSX1 gene variant rs3821949 showed an increased risk for NSCL/P in various genetic models (P < 0.0001), and the A allele exhibited a more than 4-fold increased risk among cases (OR = 4.22: 95% CI = 2.16-8.22; P < 0.0001). Our investigation found no significant difference between the rs12532 variation and NSCL/P. CONCLUSION: Our study findings suggest that MSX1 gene variants may increase predisposition to NSCL/P in the Pakistani population. Further studies comprising large samples are required to identify the genetic aetiology of NSCL/P among our people.

Hydroxyapatite-Integrated, Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance.

The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels.

Electronic structure of polypyrrole composited with a low percentage of graphene nanofiller.

The low concentration of graphene (<5%) in graphene/polypyrrole composites makes it quite challenging to devise a theoretical model for these composites. Thus, herein, we present theoretical calculations to determine the geometric electronic and optical properties of graphene/polypyrrole composites. Ribbon and sheet models of various sizes were considered for graphene. Oligopyrrole of various lengths was deposited in the graphene model in different orientations including π-stacking, tilted and vertical orientations. Theoretical calculations at the M062X/def2-SVP level revealed that π-stacking is the preferred orientation. To model a lower concentration of graphene, sandwich complexes of oligopyrrole were considered with graphene nanoribbons. Interaction energies revealed that sandwich complexes possessed superior additivity. The NCI analysis established that weak van der Waals interactions existed in all composites. Moreover, the HOMO-LUMO gap decreases as the concentration of graphene increases. Thus, the computed optical band gap of the C58H24-based composite is about 1.7 eV, which is consistent with the reported experimental value (2.1-1.81 eV). The computed band gap further decreases to ∼1.6 eV when the proportion of graphene increases to C64H26. Thus, our results for the graphene nanoribbon-based polypyrrole composites are in good agreement with experimental results. The UV/visible spectra revealed that as the concentration of graphene increases, a red shift is observed for all the configurations, which is consistent with experimental results.

Developing Wound Dressings Using 2-deoxy-D-Ribose to Induce Angiogenesis as a Backdoor Route for Stimulating the Production of Vascular Endothelial Growth Factor.

2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound dressings based on the delivery of this sugar to induce angiogenesis in chronic wounds. In this review, we will survey the small volume of conflicting literature on this and related sugars, some of which are reported to be anti-angiogenic. We review the evidence of 2dDR having the ability to stimulate a range of pro-angiogenic activities in vitro and in a chick pro-angiogenic bioassay and to stimulate new blood vessel formation and wound healing in normal and diabetic rat models. The biological actions of 2dDR were found to be 80 to 100% as effective as VEGF in addition to upregulating the production of VEGF. We then demonstrated the uptake and delivery of the sugar from a range of experimental and commercial dressings. In conclusion, its pro-angiogenic properties combined with its improved stability on storage compared to VEGF, its low cost, and ease of incorporation into a range of established wound dressings make 2dDR an attractive alternative to VEGF for wound dressing development.

Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract.

Hereditary congenital cataract (HCC) is clinically and genetically heterogeneous. We investigated HCC that segregates in three inbred families (LUCC03, LUCC16, and LUCC24). Ophthalmological examinations revealed cataracts with variability related to the age of onset segregating in a recessive manner in these families. Exome sequencing of probands identified a novel homozygous c.2710delG;p.(Val904Cysfs*36) EPHA2 variant in LUCC03 and a known homozygous c.2353G>A;p.(Ala785Thr) EPHA2 variant in the other two recessive families. EPHA2 encodes a transmembrane tyrosine kinase receptor, which is primarily involved in membrane-transport, cell-cell adhesion, and repulsion signaling processes. Computational structural modeling predicts that substitution of a threonine for an alanine p.(Ala785Thr) results in the formation of three new hydrogen bonds with the neighboring residues, which causes misfolding of EPHA2 in both scenarios. Insights from our study will facilitate counseling regarding the molecular and phenotypic landscape of EPHA2-related HCC.

P.arg102ser is a common Pde6a mutation causing autosomal recessive retinitis pigmentosa in Pakistani families.

OBJECTIVE: To explore the genetic cause of autosomal recessive retinitis pigmentosa in consanguineous families. METHODS: The multi-centre study was conducted from July 2015 to June 2018 at Liaquat University of Medical and Health Sciences, Jamshoro, the University of Sindh, Jamshoro, and Islamia University, Bahawalpur, Pakistan, and comprised families affected with non-syndromic autosomal recessive retinitis pigmentosa. Ophthalmological investigations were done to assess the fundus of the patients and the status of the disease. Pedigrees were drawn and family histories were recorded to find out the mode of inheritance. A 10cc sample of whole blood was obtained from each participant and deoxyribonucleic acid was extracted. Homozygosity mapping was performed using three short tandem repeat polymorphisms closely linked to phosphodiesterase 6A gene, and the linked families were Sanger-sequenced for identification of the mutation. Bioinformatic tools were used to design amplification refractory mutation system assay and to assess the protein structure and pathogenic effects of the mutation. RESULTS: In the 80 consanguineous families, there were 464 individuals, and, of them, 236(51%) were affected with their age ranging between 4 and 80 years. Family history and pedigree drawings revealed autosomal recessive retinitis pigmentosa with early childhood onset. Linkage analysis indicated the homozygosity in 6(7.5%) families. Sanger-sequencing revealed a common mutation c.304C>A (p.Arg102Ser); segregating with the disease in the linked families. CONCLUSION: The findings may offer effective genetic counselling and minimise disease penetration in consanguineous families.

2-deoxy-d-ribose (2dDR) upregulates vascular endothelial growth factor (VEGF) and stimulates angiogenesis.

BACKGROUND: Delayed neovascularisation of tissue-engineered (TE) complex constructs is a major challenge that causes their failure post-implantation. Although significant progress has been made in the field of angiogenesis, ensuring rapid neovascularisation still remains a challenge. The use of pro-angiogenic agents is an effective approach to promote angiogenesis, and vascular endothelial growth factor (VEGF) has been widely studied both at the biological and molecular levels and is recognised as a key stimulator of angiogenesis. However, the exogenous use of VEGF in an uncontrolled manner has been shown to result in leaky, permeable and haemorrhagic vessels. Thus, researchers have been actively seeking alternative agents to upregulate VEGF production rather than exogenous use of VEGF in TE systems. We have previously revealed the potential of 2-deoxy-d-ribose (2dDR) as an alternative pro-angiogenic agent to induce angiogenesis and accelerates wound healing. However, to date, there is not any clear evidence on whether 2dDR influences the angiogenic cascade that involves VEGF. METHODS: In this study, we explored the angiogenic properties of 2dDR either by its direct application to human aortic endothelial cells (HAECs) or when released from commercially available alginate dressings and demonstrated that when 2dDR promotes angiogenesis, it also increases the VEGF production of HAECs. RESULTS: The VEGF quantification results suggested that VEGF production by HAECs was increased with 2dDR treatment but not with other sugars, including 2-deoxy-l-ribose (2dLR) and d-glucose (DG). The stability studies demonstrated that approximately 40-50% of the 2dDR had disappeared in the media over 14 days, either in the presence or absence of HAECs, and the reduction was higher when cells were present. The concentration of VEGF in the media also fell after day 4 associated with the reduction in 2dDR. CONCLUSION: This study suggests that 2dDR (but not other sugars tested in this study) stimulates angiogenesis by increasing the production of VEGF. We conclude 2dDR appears to be a practical and effective indirect route to upregulating VEGF for several days, leading to increased angiogenesis.

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.

Design and syntheses of 7-nitro-2-aryl-4H-benzo[d][1,3]oxazin-4-ones as potent anticancer and antioxidant agents.

A group of new nitro substituted benzoxazinones (3a-k) were synthesized from easily available 4-nitroanthranilic acid. All the synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR, mass spectrometry and elemental analysis. Anti-proliferative and pro-apoptotic potential of all the synthesized compounds (3a-k) was evaluated by MTT and Hoechst 33258 staining assay respectively whereas their antioxidant properties were determined via DPPH free radical scavenging assay. The most active compounds (3a, 3c and 3k) showed significant cytotoxic potential against HeLa cells with an inhibition of cell viability that ranged between 28.54 and 44.67% (P < 0.001). Albeit statistically different, the anti-proliferative effect of 3c was in close match with that of the reference drug doxorubicin. Likewise, the test compounds showed profound pro-apoptotic potential with an apoptotic index that ranged between 52.86 and 75.61%. Besides, the docking studies revealed a higher efficiency for compounds (3a and 3h) owing to their better affinity and inhibition constant (Ki = 4.397 and 3.713 nmol) respectively. The antioxidant potential of synthesized benzoxazinones (3a-k) was in close agreement with the experimental anticancer results with a percent inhibition from 34.45 to 85.93% as compared to standard (90.56%).

In-Situ Forming pH and Thermosensitive Injectable Hydrogels to Stimulate Angiogenesis: Potential Candidates for Fast Bone Regeneration Applications.

Biomaterials that promote angiogenesis are required for repair and regeneration of bone. In-situ formed injectable hydrogels functionalised with bioactive agents, facilitating angiogenesis have high demand for bone regeneration. In this study, pH and thermosensitive hydrogels based on chitosan (CS) and hydroxyapatite (HA) composite materials loaded with heparin (Hep) were investigated for their pro-angiogenic potential. Hydrogel formulations with varying Hep concentrations were prepared by sol-gel technique for these homogeneous solutions were neutralised with sodium bicarbonate (NaHCO3) at 4 °C. Solutions (CS/HA/Hep) constituted hydrogels setting at 37 °C which was initiated from surface in 5-10 minutes. Hydrogels were characterised by performing injectability, gelation, rheology, morphology, chemical and biological analyses. Hydrogel solutions facilitated manual dropwise injection from 21 Gauge which is highly used for orthopaedic and dental administrations, and the maximum injection force measured through 19 G needle (17.191 ± 2.296N) was convenient for manual injections. Angiogenesis tests were performed by an ex-ovo chick chorioallantoic membrane (CAM) assay by applying injectable solutions on CAM, which produced in situ hydrogels. Hydrogels induced microvascularity in CAM assay this was confirmed by histology analyses. Hydrogels with lower concentration of Hep showed more efficiency in pro-angiogenic response. Thereof, novel injectable hydrogels inducing angiogenesis (CS/HA/Hep) are potential candidates for bone regeneration and drug delivery applications.

MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case control study.

BACKGROUND: To study the role of single nucleotide variants (SNVs) of genes related to preeclampsia in Pakistani pregnant women. METHODS: After ethical approval and getting informed consent; 250 pregnant women were enrolled and equally divided into two groups (125 preeclamptic cases and 125 normotensive pregnant women). Demographic details and medical history were recorded, and 10 ml blood sample was obtained for DNA extraction. The tetra-primer amplification refractory mutation system (ARMS) assays were developed for assessing the variants of three preeclampsia related genes; F5, MTHFR and VEGFA. An association of six SNVs; F5:c.1601G > A (rs6025), F5:c.6665A > G (rs6027), MTHFR: c.665C > T (rs1801133), MTHFR: c.1286A > C (rs1801131), VEGFA: c.-2055A > C (rs699947) and VEGFA: c.*237C > T (rs3025039) with preeclampsia was determined by using different genetic models. RESULTS: Genotyping of the SNVs revealed that patients with MTHFR:c.665C > T, have increased susceptibility to preeclampsia (CT versus CC/TT: OR = 2.79, 95% CI = 1.18-6.59; P* = 0.046 and CT/TT vs CC: OR = 2.91, 95% CI = 1.29-6.57; P* = 0.0497, in overdominant and dominant models, respectively), whereas F5:c.6665A > G, (A/G vs AA/GG: OR = 0.42, 95% CI = 0.21-0.84; P* = 0.038 in overdominant model) and MTHFR:c.1286A > C, (CC versus AA: OR = 0.36, 95% CI = 0.18-0.72; P* = 0.0392 in codominant model) have significantly decreased risk for preeclampsia. F5:c.1601G > A, VEGFA: c.-2055A > C and VEGFA: c.*237C > T variants revealed no relationship with the disease. CONCLUSION: This is the first case control study describing the protective role of F5:c.6665A > G against preeclampsia in any world population. In addition, the present study confirmed the association and role of MTHFR gene variations in the development of preeclampsia in Pakistani patients. Further genetic studies may be required to better understand the complex genetic mechanism of SNVs in preeclampsia related genes in pregnant women.

Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs.

Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a-3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a-3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC50 values were found in the range of 61.98 ±â€¯0.43 to 273.43 ±â€¯0.96 µM and 7-Deazaxanthine was taken as a standard inhibitor with IC50 = 38.68 ±â€¯4.42 µM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a-4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b-4g exhibited a good inhibitory potential in the range of 43.86 ±â€¯1.11-163.43 ±â€¯2.03 µM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.

Novel chitosan derivative based composite scaffolds with enhanced angiogenesis; potential candidates for healing chronic non-healing wounds.

The success of wound healing depends upon the proper growth of vascular system in time in the damaged tissues. Poor blood supply to wounded tissues or tissue engineered grafts leads to the failure of wound healing or rejection of grafts. In present paper, we report the synthesis of novel organosoluble and pro-angiogenic chitosan derivative (CSD) by the reaction of chitosan with 1,3-dimethylbarbituric acid and triethylorthoformate (TEOF). The synthesized material was characterized by FTIR and 13C-NMR to confirm the incorporated functional groups and new covalent connectivities. Biodegradability of the synthesized chitosan derivative was tested in the presence of lysozyme and was found to be comparable with CS. The cytotoxicity and apoptosis effect of new derivative was determined against gastric adenocarcinoma (AGS) cells and was found to be non-toxic. The CSD was found to be soluble in majority of organic solvents. It was blended with polycaprolactone (PCL) to form composite scaffolds. From an ex ovo CAM assay, it was noted that CSD stimulated the angiogenesis.

Novel pyridine-2,4,6-tricarbohydrazide thiourea compounds as small key organic molecules for the potential treatment of type-2 diabetes mellitus: In vitro studies against yeast α- and ß-glucosidase and in silico molecular modeling.

A range of novel pyridine-2,4,6-tricarbohydrazide thiourea compounds (4a-i) were synthesized in good to excellent yields (63-92%). The enzyme inhibitory potentials of these compounds were investigated against α- and ß-glucosidases because these enzymes play a crucial role in treating type-2 diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC50 38.22 ± 0.12 µM), compounds 4i (IC50 25.49 ± 0.67 µM), 4f (IC50 28.91 ± 0.43 µM), 4h (IC50 30.66 ± 0.52 µM), and 4e (IC50 35.01 ± 0.45 µM) delivered better inhibition against α-glucosidase and were quite inactive/completely inactive against ß-glucosidase. The structure-activity relationship of these compounds was developed and elaborated with the help of molecular docking studies.

In vitro modulatory effects of functionalized pyrimidines and piperidine derivatives on Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) activities.

The development of biologically active molecules based on molecular recognition is an attractive and challenging task in medicinal chemistry and the molecules that can activate/deactivate certain receptors are of great medical interest. In this contribution, selected pyrimidine/piperidine derivatives were synthesized and tested for the ability to activate/deactivate Aryl hydrocarbon receptor (AhR) and Glucocorticoid receptor (GR). Tested compounds are shown to activate the receptors but to much lesser extent than positive controls, dioxin and dexamethasone for Ahr and GR, respectively. However, some of them antagonized the positive controls action. Although further in vivo studies are needed to fully characterize the bioactivities of these compounds, the reported in vitro evidences demonstrate that they might be used as the modulators of AhR and GR activities.

An Efficient Synthesis of bi-Aryl Pyrimidine Heterocycles: Potential New Drug Candidates to Treat Alzheimer's Disease.

A series of 13 novel pyrimidine-based sulfonamides 6a-m were synthesized in short periods of time under microwave conditions in good to excellent yield (54-86%). The chemical structures of these heterocycles consist of a central pyrimidine ring having a phenyl group and pyrimidine groups with sulfonamide motifs. The enzyme inhibitory potential of these compounds was investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) because these enzymes play a crucial role in the treatment of Alzheimer's disease. As compared to the reference compound eserine (IC50 = 0.04 ± 0.0001 µM for AChE and IC50 = 0.85 ± 0.0001 µM for BChE), the IC50 values of the synthesized compounds ranged from 3.73 ± 0.61 µM to 57.36 ± 0.22 µM for AChE and 4.81 ± 0.16 µM to 111.61 ± 0.53 µM for BChE. Among these tested compounds, 6j having a -CH3 group was found to be the most potent one against both enzymes (AChE, IC50 = 3.73 ± 0.61 µM; BChE, IC50 = 4.81 ± 0.16 µM). Quantitative structure-activity relationship (QSAR) and molecular docking studies of the synthesized compounds were also performed.

A Fair Contention Access Scheme for Low-Priority Traffic in Wireless Body Area Networks.

Recently, wireless body area networks (WBANs) have attracted significant consideration in ubiquitous healthcare. A number of medium access control (MAC) protocols, primarily derived from the superframe structure of the IEEE 802.15.4, have been proposed in literature. These MAC protocols aim to provide quality of service (QoS) by prioritizing different traffic types in WBANs. A contention access period (CAP)with high contention in priority-based MAC protocols can result in higher number of collisions and retransmissions. During CAP, traffic classes with higher priority are dominant over low-priority traffic; this has led to starvation of low-priority traffic, thus adversely affecting WBAN throughput, delay, and energy consumption. Hence, this paper proposes a traffic-adaptive priority-based superframe structure that is able to reduce contention in the CAP period, and provides a fair chance for low-priority traffic. Simulation results in ns-3 demonstrate that the proposed MAC protocol, called traffic- adaptive priority-based MAC (TAP-MAC), achieves low energy consumption, high throughput, and low latency compared to the IEEE 802.15.4 standard, and the most recent priority-based MAC protocol, called priority-based MAC protocol (PA-MAC).