Physicochemical Properties and Simulation of Magnesium/Zinc Binary-Substituted Hydroxyapatite with Enhanced Biocompatibility and Antibacterial Ability.

Ionic substitution can effectively activate the surface of hydroxyapatite (HA) for bone repair and regeneration processes. Therefore in this study, magnesium (Mg)-, zinc (Zn)-, and Mg/Zn-codoped HA was prepared by a hydrothermal method. The results of experimental and first-principles calculations verify the existence of Mg and Zn ions in the HA structure by altering cell parameters, crystallinity, and particle size. The results also showed that Mg and Zn are actively accommodated at the Ca(1) and Ca(2) positions, which not only inhibit HA formation but also promote calcium-deficient HA, and when the codoping content increased to 10%Mg and 10%Zn, the HA transformed completely to the whitlockite phase. Furthermore, the impact of codoping on biocompatibility was examined by employing MC3T3 cells. The in vitro study revealed that 5%Mg and 5%Zn single and -codoped HA promoted the proliferation of MC3T3 cells and 5%Mg-doped and -codoped HA stimulated MC3T3 cell differentiation, while 5%Zn-doped and -codoped HA revealed worthy antibacterial properties. Overall, the obtained results demonstrate that cosubstituted HA (5%Mg and 5%Zn) is promising, which not only eradicates bacteria (Escherichia coli and Staphylococcus aureus) but also induces bone regeneration. These findings suggest that 5%Mg and 5%Zn binary-substituted HA is a very promising biomaterial for hard tissue scaffolds and bone repair.

Novel flurbiprofen clubbed oxadiazole derivatives as potential urease inhibitors and their molecular docking study.

In this study, twenty eight novel oxadiazole derivatives (5-32) of the marketed available non-steroidal anti-inflammatory drug (NSAID), (S)-flurbiprofen (1), were synthesized via I2 mediated cyclo-addition reaction in better yields. The synthesized hydrazone-Schiff bases were cyclized with iodine by using potassium hydroxide as a base in DMSO solvent to obtain oxadiazole derivatives (5-32). Structures of the synthesized products were confirmed with HR-ESI-MS, 1H-NMR spectroscopy and CHN analysis. After structure confirmations all analogs were evaluated for urease (in vitro) inhibitory activity. Amongst the series, fourteen compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 were found to be excellent inhibitors of urease enzyme, having IC50 values of 12 ± 0.9 to 20 ± 0.5 µM, better than the standard thiourea (IC50 = 22 ± 2.2 µM), whereas the remaining fourteen derivatives displayed good to moderate activity. The in silico study was executed to analyse the interaction between the active site of the enzyme (urease) and the produced compounds. The docking study revealed that compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 had lower docking scores than the standard compound thiourea and revealed better interactions with the urease enzyme.

Association of Computed Tomography Measures of Muscle and Adipose Tissue and Progressive Changes throughout Treatment with Clinical Endpoints in Patients with Advanced Lung Cancer Treated with Immune Checkpoint Inhibitors.

To investigate the association between skeletal muscle mass and adiposity measures with disease-free progression (DFS) and overall survival (OS) in patients with advanced lung cancer receiving immunotherapy, we retrospectively analysed 97 patients (age: 67.5 ± 10.2 years) with lung cancer who were treated with immunotherapy between March 2014 and June 2019. From computed tomography scans, we assessed the radiological measures of skeletal muscle mass, and intramuscular, subcutaneous and visceral adipose tissue at the third lumbar vertebra. Patients were divided into two groups based on specific or median values at baseline and changes throughout treatment. A total number of 96 patients (99.0%) had disease progression (median of 11.3 months) and died (median of 15.4 months) during follow-up. Increases of 10% in intramuscular adipose tissue were significantly associated with DFS (HR: 0.60, 95% CI: 0.38 to 0.95) and OS (HR: 0.60, 95% CI: 0.37 to 0.95), while increases of 10% in subcutaneous adipose tissue were associated with DFS (HR: 0.59, 95% CI: 0.36 to 0.95). These results indicate that, although muscle mass and visceral adipose tissue were not associated with DFS or OS, changes in intramuscular and subcutaneous adipose tissue can predict immunotherapy clinical outcomes in patients with advanced lung cancer.

Daphne mucronata enhances cell proliferation and protects human adipose stem cells against monosodium iodoacetate induced oxidative stress in vitro.

Mesenchymal stem cells (MSCs) are being used to treat many diseases as they exhibit great regenerative potential. However, MSC's transplantation sometimes does not yield the maximum regenerative outcome as they are unable to survive in inflammatory conditions. Several approaches including preconditioning are used to improve the survival rate of mesenchymal stem cells. One such recently reported approach is preconditioning MSCs with plant extracts. The present study was designed to evaluate the effect of Daphne mucronata extract on stressed human adipose-derived mesenchymal stem cells (hADMSCs). Isolated hADMSCs were preconditioned with different concentrations of Daphne muconata extract and the protective, proliferative, antioxidant and anti-inflammatory effect was assessed through various assays and expression analysis of inflammatory markers regulated through NF-κB pathway. Results suggest that preconditioning hADMSCs with Daphne mucronata increased the cell viability, proliferative and protective potential of hADMSCs with a concomitant reduction in LDH, ROS and elevation in SOD activity. Moreover, both the ELISA and gene expression analysis demonstrated down regulations of inflammatory markers (IL1-ß, TNF-α, p65, p50, MMP13) in Daphne mucronata preconditioned hADMSCs as compared to stress. This is the first study to report the use of MIA induced oxidative stress against hADMSC's and effect of Daphne mucronata on stressed hADMSCs. Results of these studies provided evidence that Daphne mucronata protects the hADMSCs during stress conditions by down regulating the inflammatory markers and hence increase the viability and proliferative potential of hADMSCs that is crucial for transplantation purposes.

Impact of city effluents on water quality of Indus River: assessment of temporal and spatial variations in the southern region of Khyber Pakhtunkhwa, Pakistan.

The impact of city effluents on water quality of Indus River was assessed in the southern region of Khyber Pakhtunkhwa, Pakistan. Water samples were collected in dry (DS) and wet (WS) seasons from seven sampling zones along Indus River and the physical, bacteriological, and chemical parameters determining water quality were quantified. There were marked temporal and spatial variations in the water quality of Indus River. The magnitude of pollution was high in WS compared with DS. The quality of water varied across the sampling zones, and it greatly depended upon the nature of effluents entering the river. Water samples exceeded the WHO permissible limits for pH, EC, TDS, TS, TSS, TH, DO, BOD, COD, total coliforms, Escherichia coli, Ca2+, Mg2+, NO3-, and PO42-. Piper analysis indicated that water across the seven sampling zones along Indus River was alkaline in nature. Correlation analyses indicated that EC, TDS, TS, TH, DO, BOD, and COD may be considered as key physical parameters, while Na+, K+, Ca2+, Mg2+, Cl-, F-, NO3-, PO42-, and SO42- as key chemical parameters determining water quality, because they were strongly correlated (r > 0.70) with most of the parameters studied. Cluster analysis indicated that discharge point at Shami Road is the major source of pollution impairing water quality of Indus River. Wastewater treatment plants must be installed at all discharge points along Indus River for protecting the quality of water of this rich freshwater resource in Pakistan.

Assessing impact of effluent discharge on irrigation water quality in southern region of Khyber Pakhtunkhwa, Pakistan.

Chemical quality and extent of pollution in effluent-contaminated irrigation water collected from two sectors (X and Y) of peri-urban southern regions of Khyber Pakhtunkhwa, Pakistan, were investigated. Various physico-chemical parameters like pH, EC, TS, TSS, TDS, TH, cations (Na1+, K1+, Li1+, Ca2+, Mg2+), anions (Cl1-, F1-, HCO31-, NO31-, SO42-), and heavy metals (Cr, Fe, Cu, Zn, Pb, Cd) were determined. The data indicated wide ranges of variation in all the parameters. Concentration of physico-chemical properties such as EC, TS, TSS, TH, Li1+, Ca2+, Mg2+, and HCO31- and heavy metals (Cr, Fe, Cu, and Cd) exceeded WHO permissible limits. The distribution of heavy metals in two sampling areas followed the increasing order as Fe > Cr > Cd > Cu > Pb > Zn. The Piper diagram showed that water in the region was of alkaline type. Strong positive correlations were observed among most of the parameters; however, pH was negatively correlated with most of the parameters. According to principle component analysis, parameters causing variations in water quality were mainly EC, TDS, TS, TSS, TH, Na1+, K1+, Ca2+, Mg2+, F1-, NO31-, SO42-, Cr, Fe, Cu, and Zn. Linear regression analysis revealed that heavy metals like Cr, Fe, and Cu concentrations were strongly correlated having an R 2 value of 0.92 at P ≤ 0.001 with pH. Overall, the results suggested that irrigation water of the area was not fit for irrigation purposes and might cause serious threats for safe, healthy food and feed production. Proper monitoring of water of the said area should be carried out, and quality of irrigation water should be checked from time to time.

Socio-cultural and Knowledge-Based Barriers to Tuberculosis Diagnosis for Women in Bhopal, India.

BACKGROUND: In India, only one woman is diagnosed with tuberculosis (TB) for every 2.4 men. Previous studies have indicated gender disparities in care-seeking behavior and TB diagnosis; however, little is known about the specific barriers women face. OBJECTIVES: This study aimed to characterize socio-cultural and knowledge-based barriers that affected TB diagnosis for women in Bhopal, India. MATERIALS AND METHODS: In-depth interviews were conducted with 13 affected women and 6 health-care workers. The Bhopal Diagnostic Microscopy Laboratory Register (n = 121) and the Bhopal district report (n = 261) were examined for diagnostic and care-seeking trends. RESULTS: Women, especially younger women, faced socio-cultural barriers and stigma, causing many to hide their symptoms. Older women had little awareness about TB. Women often sought treatment from private practitioners, resulting in delayed diagnosis. CONCLUSIONS: Understanding these diagnostic and help-seeking behaviors barriers for women is critical for development of a gender-sensitive TB control program.

Synthesis, characterization, DNA binding and in vitro antimicrobial studies of a novel tetra-substituted N-isopropyl-N-(4-ferrocenylphenyl)-N'-(2,6-diethylphenyl)-N″-benzoylguanidine: crystallographic structure and quantum chemical computations.

A novel tetra-substituted guanidine, N-isopropyl-N-(4-ferrocenylphenyl)-N'-(2,6-diethylphenyl)-N″-benzoylguanidine (1), [(CH3)2CH)(C5H5FeC5H4C6H4)NC(NHCOC6H5)(NHC6H3(CH2CH3)2] has been synthesized and characterized by elemental analysis, FT-IR, multinuclear ((1)H, (13)C) NMR spectroscopy, single crystal X-rays diffraction analysis and density functional theory based quantum chemical calculations. The torsion angles indicating that the guanidine moiety and carbonyl group are almost co-planar, due to the pseudo hexagonal ring formed by intramolecular N-H⋯O hydrogen bonds. The DNA interaction studies performed by cyclic voltammetry and UV-visible spectroscopy are in close agreement with the binding constants (K) 1.4×10(4) and 1.2×10(4) respectively. The shift in peak potential, current and absorption maxima of the studied ferrocenyl guanidine in the presence of DNA discovered that CV coupled with UV-vis spectroscopy could provide an opportunity to elaborate DNA interaction mechanism, a prerequisite for the design of new drug like agents and understanding the molecular basis of their action. The synthesized compound (1) has also been screened for their antibacterial and antifungal.

Ferrocene-based guanidine derivatives: in vitro antimicrobial, DNA binding and docking supported urease inhibition studies.

Some novel ferrocenyl guanidines 1-8 were synthesized and characterized by different spectroscopic methods, elemental analysis and single crystal X-rays diffraction techniques. The crystallographic studies revealed that the existence of the strong non-bonding interactions facilitate these molecules to interact with biological macro-molecules like DNA that described to inherit good biological activities. The DNA interaction studies carried out by cyclic voltammetry (CV) and UV-visible spectroscopy are in close agreement with the binding constants (K) (0.79-5.4) × 10(5) (CV) and (0.72-5.1) × 10(5) (UV-vis). The shift in peak potential, current and absorption maxima of the studied ferrocenyl guanidines in the presence of DNA revealed that CV coupled with UV-vis spectroscopy could provide an opportune to characterize metal-based compounds-DNA interaction mechanism, a prerequisite for the design of new anticancer agents and understanding the molecular basis of their action. The compounds 1-8 have been screened for their antibacterial, antifungal and urease inhibition potency. A concurrent in silico study has also been applied on ferrocene moiety impregnated guanidines 1-8 to identify most active compounds having for inhibiting the activity of urease (pdb id 3LA4). Most of the compounds were found as potent inhibitors of urease and the compound 1 was found to be the most active with an IC50 of 16.83 ± 0.03 µM. The docking scores are in close agreement with the in vitro obtained IC50 values of inhibitors 1-8.

Vasoactive intestinal peptide modulation of the steroid-induced LH surge involves kisspeptin signaling in young but not in middle-aged female rats.

Age-related LH surge dysfunction in middle-aged rats is characterized, in part, by reduced responsiveness to estradiol (E2)-positive feedback and reduced hypothalamic kisspeptin neurotransmission. Vasoactive intestinal peptide (VIP) neurons in the suprachiasmatic nucleus project to hypothalamic regions that house kisspeptin neurons. Additionally, middle-age females express less VIP mRNA in the suprachiasmatic nucleus on the day of the LH surge and intracerebroventricular (icv) VIP infusion restores LH surges. We tested the hypothesis that icv infusion of VIP modulates the LH surge through effects on the kisspeptin and RFamide-related peptide-3 (RFRP-3; an estradiol-regulated inhibitor of GnRH neurons) neurotransmitter systems. Brains were collected for in situ hybridization analyses from ovariectomized and ovarian hormone-primed young and middle-aged females infused with VIP or saline. The percentage of GnRH and Kiss1 cells coexpressing cfos and total Kiss1 mRNA were reduced in saline-infused middle-aged compared with young females. In young females, VIP reduced the percentage of GnRH and Kiss1 cells coexpressing cfos, suggesting that increased VIP signaling in young females adversely affected the function of Kiss1 and GnRH neurons. In middle-aged females, VIP increased the percentage of GnRH but not Kiss1 neurons coexpressing cfos, suggesting VIP affects LH release in middle-aged females through kisspeptin-independent effects on GnRH neurons. Neither reproductive age nor VIP affected Rfrp cell number, Rfrp mRNA levels per cell, or coexpression of cfos in Rfrp cells. These data suggest that VIP differentially affects activation of GnRH and kisspeptin neurons of female rats in an age-dependent manner.

Preliminary investigation of anticancer activity by determining the DNA binding and antioxidant potency of new ferrocene incorporated N,N',N″-trisubstituted phenylguanidines.

Six new bioactive ferrocene based phenylguanidines were successively synthesized and characterized by means of various analytical techniques like elemental analysis, FT-IR, multinuclear ((1)H and (13)C) NMR, UV-Vis spectroscopy and cyclic voltammetry. The interaction of compounds with DNA was investigated by spectroscopic and cyclic voltammetric measurements. The interaction was found to be the electrostatic and the binding constants values were impressively larger. Compounds f-1, f-2, f-3 have slight larger binding constant values ranging from 0.8×10(5) to 2.4×10(5) as compared to g-1, g-2 and g-3 ranging from 7.6×10(4) to 1.1×10(5) which is most probably due to the presence of ferrocene at para position where the delocalization of electrons is maximum. Antioxidant activity was determined by UV-Vis spectrophotometer by using DPPH as a free radical. All the compounds exhibit good antioxidant activity and the results so obtained support the structure activity relationship.

2-(3-Chloro-benzo-yl)-3-(3,4-di-chloro-phen-yl)-1-(4-ferrocenylphen-yl)guanidine.

In the title compound, [Fe(C5H5)(C25H17Cl3N3O)], the isolated cyclo-penta-dienyl (Cp) ring is disordered over two set of sites in a 0.577 (8):0.423 (8) ratio. The dihedral angle between the other Cp ring and its attached benzene ring is 13.6 (3)°, and that between the benzene ring and the guanidine group is 64.8 (2)°. One of the N-H groups forms both an intra- and an inter-molecular N-H⋯O hydrogen bond; the other N-H group does not form any hydrogen bonds. In the crystal, pairs of the inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers.

5-(4-Chloro-phen-yl)-2-fluoro-pyridine.

In the title compound, C(11)H(7)ClFN, the chloro-benzene and 2-fluoro-pyridine rings are oriented at a dihedral angle of 38.83 (5)°. In the crystal, there are no hydrogen-bonding interactions.

N-[(Methyl-sulfan-yl)meth-yl]benzamide.

In the title compound, C(9)H(11)NOS, the phenyl ring and formamide unit make a dihedral angle of 23.93 (14)°, whereas the (methyl-sulfan-yl)methyl group is oriented at a dihedral angle of 61.31 (8)° with respect to the phenyl ring. There are inter-molecular N-H⋯O hydrogen bonds, forming C(4) chains along the [010] direction. These polymeric chains are linked by C-H⋯O hydrogen bonds to form polymeric sheets in the (110) plane.

Anterior face-lift for correction of middle face aging utilizing a minimally invasive technique.

OBJECTIVE: A minimally invasive face-lifting approach aimed at rejuvenation of the midface was examined, for patients with concerns limited to midfacial aging. METHODS: An incision in the preauricular area and then minor undermining to lift superfical musculo apponeurotic system (SMAS), followed by SMAS plication and removal of skin laxity in the midface, results in excellent superolateral reversal of inferomedial displacement of the aging vector. RESULTS AND CONCLUSION: A minimally invasive procedure was performed easily under local anesthesia in an office/ambulatory surgery center setting.

Fibroblast migration on fibronectin requires three distinct functional domains.

Mesenchymal cell movement is normally constrained; however, fibronectin can provide a pathway for stromal cell migration during embryogenesis, morphogenesis, and wound healing. Cells can adhere to fibronectin via integrin and nonintegrin receptors, which bind multiple unique peptide sequences. Synthetic peptides and recombinant proteins were used to delineate the functional domains needed for human fibroblast migration over fibronectin. The 9th and 10th fibronectin type III repeats, which contain RGD and PHSRN synergy cell attachment sequences, support almost maximal fibroblast attachment, but not migration of primary dermal fibroblasts. Specific sequences within the heparin domain and the IIICS region are also required for migration. These findings predict and additional data confirm the necessity for the cooperation of multiple integrin and nonintegrin receptors for fibroblast migration on fibronectin. Such stringency of migration most likely imposes an immense constraint on normal mesenchymal cell mobility in unperturbed tissue. Loss of such restraint may be critical for the migration cancer cells through the extracellular matrix.

Resuspension of mild to moderate jawline laxity using a minimally invasive technique.

BACKGROUND: A practical approach for superficial musculoapponeurotic system plication and neck lift is indicated for early aging changes of jawline. METHODS: A single or series of small punches or single incisions at the earlobe and then minor undermining to lift the superficial musculoapponeurotic system followed by removal of skin laxity in neck and jowl result in a seamless scar via a simple V to Y closure. RESULTS AND CONCLUSION: A minimally invasive procedure was performed easily under local anesthesia in an office/ambulatory surgery center setting.

Experience with more than 5,000 cases in which monitored anesthesia care was used for liposuction surgery.

BACKGROUND: Conscious sedation using monitored anesthesia care can provide a clinical spectrum from relaxation to moderate anesthesia. This middle ground between general anesthesia and "pure" tumescent liposuction can help facilitate patient comfort and surgical proficiency during the procedure. OBJECTIVE: To describe a method of liposuction surgery with monitored anesthesia care in which a designated licensed and qualified individual is responsible for administration of supplemental intravenous conscious sedation as well as continuous monitoring of the patient. METHODS: Conscious sedation is induced with midazolam, and the patient is titrated to level II-V on the Ramsey sedation scale with propofol. The basic surgical technique is that of tumescent liposuction. However, the supplemental conscious sedation allows the tumescent fluid to be infiltrated at higher rates and fat extraction to be completed in a shorter period with minimal or no discomfort. RESULTS: In the authors' experience with more than 5,000 cases of liposuction surgery using this method, safety and efficacy have been proved. No patients have experienced significant adverse effects. CONCLUSION: Tumescent liposuction surgery with monitored anesthesia care provides a middle ground between general anesthesia and purely tumescent liposuction.