Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.

The burden of chronic diseases and patients' preference for healthcare services among adult patients suffering from chronic diseases in Bangladesh.

BACKGROUND: Low- and middle-income countries (LMICs) have a disproportionately high burden of chronic diseases, with inequalities in health care access and quality services. This study aimed to assess patients' preferences for healthcare services for chronic disease management among adult patients in Bangladesh. METHODS: The present analysis was conducted among 10,385 patients suffering from chronic diseases, drawn from the latest Household Income and Expenditure Survey 2016-2017. We used the multinomial logistic regression to investigate the association of chronic comorbid conditions and healthcare service-related factors with patients' preferences for healthcare services. RESULTS: The top four dimensions of patient preference for healthcare services in order of magnitude were quality of treatment (30.3%), short distance to health facility (27.6%), affordability of health care (21.7%) and availability of doctors (11.0%). Patients with heart disease had a 29% significantly lower preference for healthcare affordability than the quality of healthcare services (relative risk ratio [RRR] = 0.71; 0.56-0.90). Patients who received healthcare services from pharmacies or dispensaries were more likely to prefer a short distance to a health facility (RRR = 6.99; 4.80-9.86) or affordability of healthcare services (RRR = 3.13; 2.25-4.36). Patients with comorbid conditions were more likely to prefer healthcare affordability (RRR = 1.39; 1.15-1.68). In addition, patients who received health care from a public facility had 2.93 times higher preference for the availability of medical doctors (RRR = 2.93; 1.70-5.04) than the quality of treatment in the health facility, when compared with private service providers. CONCLUSIONS: Patient preferences for healthcare services in chronic disease management were significantly associated with the type of disease and its magnitude and characteristics of healthcare providers. Therefore, to enhance service provision and equitable distribution and uptake of health services, policymakers and public health practitioners should consider patient preferences in designing national strategic frameworks for chronic disease management. PATIENT OR PUBLIC CONTRIBUTION: Our research team includes four researchers (co-authors) with chronic diseases who have experience of living or working with people suffering from chronic conditions or diseases.

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu.

Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at their respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two closely related MMPs: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and gene expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus and functions in calcium regulation, contractile dysfunction, gene expression and ribosomal RNA transcription. Our particular interest lies in the roles MMP-2 and MT1-MMP serve within the nucleus, as they may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies for cancer and other diseases.

RYBP Sensitizes Cancer Cells to PARP Inhibitors by Regulating ATM Activity.

Ring1 and YY1 Binding Protein (RYBP) is a member of the non-canonical polycomb repressive complex 1 (PRC1), and like other PRC1 members, it is best described as a transcriptional regulator. Previously, we showed that RYBP, along with other PRC1 members, is also involved in the DNA damage response. RYBP inhibits recruitment of breast cancer gene 1(BRCA1) complex to DNA damage sites through its binding to K63-linked ubiquitin chains. In addition, ataxia telangiectasia mutated (ATM) kinase serves as an important sensor kinase in early stages of DNA damage response. Here, we report that overexpression of RYBP results in inhibition in both ATM activity and recruitment to DNA damage sites. Cells expressing RYBP show less phosphorylation of the ATM substrate, Chk2, after DNA damage. Due to its ability to inhibit ATM activity, we find that RYBP sensitizes cancer cells to poly-ADP-ribose polymerase (PARP) inhibitors. Although we find a synergistic effect between PARP inhibitor and ATM inhibitor in cancer cells, this synergy is lost in cells expressing RYBP. We also show that overexpression of RYBP hinders cancer cell migration through, at least in part, ATM inhibition. We provide new mechanism(s) by which RYBP expression may sensitize cancer cells to DNA damaging agents and inhibits cancer metastasis.

Static and Dynamic Gradient Based Directional Transportation of Neutral Molecules in Swollen Polymer Films.

Materials which selectively transport molecules offer powerful opportunities for concentrating and separating chemical agents. Here, utilizing static and dynamic chemical gradients, transport of molecules within swollen crosslinked polymers is demonstrated. Using an ≈200 µm static hydroxyl to hexyl gradient, the neutral ambipolar nerve agent surrogate diethyl (cyanomethyl)phosphonate (DECP) is directionally transported and concentrated 60-fold within 4 hours. To accelerate transport kinetics, a dynamic gradient (a "travelling wave") is utilized. Here, the non-polar dye pyrene was transported. The dynamic gradient is generated by an ion exchange process triggered by the localized introduction of an aqueous NaCl solution, which converts the gel from hydrophobic to hydrophilic. As the hydrophilic region expands, associated water enters the gel, and pyrene is pushed ahead of the expansion front. The dynamic gradient provides about 10-fold faster transport kinetics than the static gradient.

Awareness of Mouth Cancer Among Adult Dental Patients Attending the Kuwait University Dental School Clinic.

In Kuwait, the age-standardized incidence rate (per 100,000) for oral cancer is 1.5 and the mortality rate is 0.4. Early detection of oral cancer combined with appropriate treatment greatly improves the chances of cure and the quality of life. However, little is known about patient awareness of this disease and the ability to identify early signs, particularly among high-risk groups. Hence, the aim of this study is to assess dental patients' awareness and knowledge of mouth cancer and beliefs and perceptions about risk factors. A self-administered questionnaire was used to collect information from a convenience sample of outpatients attending the dental admission clinic. The questionnaire included questions to ascertain information on socio-demographic characteristics, knowledge of risk factors, and signs of oral cancer as well as sources of information regarding the same. Data were analyzed using the Statistical Package for the Social Sciences for Windows 19.0. A total of 160 questionnaires were distributed out of which 136 completed questionnaires were returned and used for the study. The mean knowledge score for oral cancer risk factors was found to be 5.2 ± 2.7 out of ten while that of signs and symptoms was 3.4 ± 2.7 out of eight. When the knowledge of risk factors of oral cancer was taken into consideration along with variables, significant difference was seen only in sex with women having better knowledge (p = 0.03). Knowledge about signs and symptoms of oral cancer revealed a highly significant difference with the level of education (p = 0.03). Family, friends, and colleagues were mentioned as the main source of information regarding oral cancer. Our findings suggest that knowledge regarding oral cancer risk factors, signs, and symptoms was found to be lacking among the dental patients which emphasizes the need for patient education at the dental centers as well as public awareness programs.

Dynamic Gradient Directed Molecular Transport and Concentration in Hydrogel Films.

Materials which selectively transport molecules along defined paths offer new opportunities for concentrating, processing and sensing chemical and biological agents. Here, we present the use of traveling ionic waves to drive molecular transport and concentration of hydrophilic molecules entrained within a hydrogel. The traveling ionic wave is triggered by the spatially localized introduction of ions, which through a dissipative ion exchange process, converts quaternary ammonium groups in the hydrogel from hydrophilic to hydrophobic. Through a reaction-diffusion process, the hydrophobic region expands with a sharp transition at the leading edge; it is this sharp gradient in hydrophilicity that drives the transport of hydrophilic molecules dispersed within the film. The traveling wave moved up to 450 µm within 30 min, while the gradient length remained 20 µm over this time. As an example of the potential of molecular concentration using this approach, a 70-fold concentration of a hydrophilic dye was demonstrated.

Matrix metalloproteinase-2 in oncostatin M-induced sarcomere degeneration in cardiomyocytes.

Cardiomyocyte dedifferentiation may be an important source of proliferating cardiomyocytes facilitating cardiac repair. Cardiomyocyte dedifferentiation and proliferation induced by oncostatin-M (OSM) is characterized by sarcomere degeneration. However, the mechanism underlying sarcomere degeneration remains unclear. We hypothesized that this process may involve matrix metalloproteinase-2 (MMP-2), a key protease localized at the sarcomere in cardiomyocytes. We tested the hypothesis that MMP-2 is involved in the sarcomere degeneration that characterizes cardiomyocyte dedifferentiation. Confocal immunofluorescence and biochemical methods were used to explore the role of MMP-2 in OSM-induced dedifferentiation of neonatal rat ventricular myocytes (NRVM). OSM caused a concentration- and time-dependent loss of sarcomeric α-actinin and troponin-I in NRVM. Upon OSM-treatment, the mature sarcomere transformed to a phenotype resembling a less-developed sarcomere, i.e., loss of sarcomeric proteins and Z-disk transformed into disconnected Z bodies, characteristic of immature myofibrils. OSM dose dependently increased MMP-2 activity. Both the pan-MMP inhibitor GM6001 and the selective MMP-2 inhibitor ARP 100 prevented sarcomere degeneration induced by OSM treatment. OSM also induced NRVM cell cycling and increased methyl-thiazolyl-tetrazolium (MTT) staining, preventable by MMP inhibition. These results suggest that MMP-2 mediates sarcomere degeneration in OSM-induced cardiomyocyte dedifferentiation and thus potentially contributes to cardiomyocyte regeneration.

Detection of Explosive Vapors: The Roles of Exciton and Molecular Diffusion in Real-Time Sensing.

Time-resolved quartz crystal microbalance with in situ fluorescence measurements are used to monitor the sorption of the nitroaromatic (explosive) vapor, 2,4-dinitrotoluene (DNT) into a porous pentiptycene-containing poly(phenyleneethynylene) sensing film. Correlation of the nitroaromatic mass uptake with fluorescence quenching shows that the analyte diffusion follows the Case-II transport model, a film-swelling-limited process, in which a sharp diffusional front propagates at a constant velocity through the film. At a low vapor pressure of DNT of ≈16 ppb, the analyte concentration in the front is sufficiently high to give an average fluorophore-analyte separation of ≈1.5 nm. Hence, a long exciton diffusion length is not required for real-time sensing in the solid state. Rather the diffusion behavior of the analyte and the strength of the binding interaction between the analyte and the polymer play first-order roles in the fluorescence quenching process.

New Oligocene primate from Saudi Arabia and the divergence of apes and Old World monkeys.

It is widely understood that Hominoidea (apes and humans) and Cercopithecoidea (Old World monkeys) have a common ancestry as Catarrhini deeply rooted in Afro-Arabia. The oldest stem Catarrhini in the fossil record are Propliopithecoidea, known from the late Eocene to early Oligocene epochs (roughly 35-30 Myr ago) of Egypt, Oman and possibly Angola. Genome-based estimates for divergence of hominoids and cercopithecoids range into the early Oligocene; however, the mid-to-late Oligocene interval from 30 to 23 Myr ago has yielded little fossil evidence documenting the morphology of the last common ancestor of hominoids and cercopithecoids, the timing of their divergence, or the relationship of early stem and crown catarrhines. Here we describe the partial cranium of a new medium-sized (about 15-20 kg) fossil catarrhine, Saadanius hijazensis, dated to 29-28 Myr ago. Comparative anatomy and cladistic analysis shows that Saadanius is an advanced stem catarrhine close to the base of the hominoid-cercopithecoid clade. Saadanius is important for assessing competing hypotheses about the ancestral morphotype for crown catarrhines, early catarrhine phylogeny and the age of hominoid-cercopithecoid divergence. Saadanius has a tubular ectotympanic but lacks synapomorphies of either group of crown Catarrhini, and we infer that the hominoid-cercopithecoid split happened later, between 29-28 and 24 Myr ago.

Extramitochondrial domain rich in carbonic anhydrase activity improves myocardial energetics.

CO2 is produced abundantly by cardiac mitochondria. Thus an efficient means for its venting is required to support metabolism. Carbonic anhydrase (CA) enzymes, expressed at various sites in ventricular myocytes, may affect mitochondrial CO2 clearance by catalyzing CO2 hydration (to H(+) and HCO3(-)), thereby changing the gradient for CO2 venting. Using fluorescent dyes to measure changes in pH arising from the intracellular hydration of extracellularly supplied CO2, overall CA activity in the cytoplasm of isolated ventricular myocytes was found to be modest (2.7-fold above spontaneous kinetics). Experiments on ventricular mitochondria demonstrated negligible intramitochondrial CA activity. CA activity was also investigated in intact hearts by (13)C magnetic resonance spectroscopy from the rate of H(13)CO3(-) production from (13)CO2 released specifically from mitochondria by pyruvate dehydrogenase-mediated metabolism of hyperpolarized [1-(13)C]pyruvate. CA activity measured upon [1-(13)C]pyruvate infusion was fourfold higher than the cytoplasm-averaged value. A fluorescent CA ligand colocalized with a mitochondrial marker, indicating that mitochondria are near a CA-rich domain. Based on immunoreactivity, this domain comprises the nominally cytoplasmic CA isoform CAII and sarcoplasmic reticulum-associated CAXIV. Inhibition of extramitochondrial CA activity acidified the matrix (as determined by fluorescence measurements in permeabilized myocytes and isolated mitochondria), impaired cardiac energetics (indexed by the phosphocreatine-to-ATP ratio measured by (31)P magnetic resonance spectroscopy of perfused hearts), and reduced contractility (as measured from the pressure developed in perfused hearts). These data provide evidence for a functional domain of high CA activity around mitochondria to support CO2 venting, particularly during elevated and fluctuating respiratory activity. Aberrant distribution of CA activity therefore may reduce the heart's energetic efficiency.

Postresuscitation administration of doxycycline preserves cardiac contractile function in hypoxia-reoxygenation injury of newborn piglets*.

OBJECTIVE: Cardiac injury is common in asphyxiated neonates and is associated with matrix metalloproteinase-2 activation. Although studies have demonstrated the cardioprotective effects of matrix metalloproteinase inhibition, this has not been tested in clinically translatable models of hypoxia-reoxygenation injury. We aimed to elucidate the effect of doxycycline, a matrix metalloproteinase inhibitor, on cardiac injury and functional recovery in a swine model of neonatal hypoxia-reoxygenation. DESIGN: Thirty-three newborn piglets were acutely instrumented for continuous monitoring of cardiac output and systemic arterial pressure. After stabilization, normocapnic alveolar hypoxia (10-15% oxygen) was instituted for 2 hours followed by 4 hours of normoxic reoxygenation. Piglets were blindly, block randomized to receive IV boluses of normal saline (control) and doxycycline at 5 minutes of reoxygenation (n = 7/group). Sham-operated piglets (n = 5) received no hypoxia-reoxygenation. Markers of myocardial injury (plasma and myocardial tissue troponin I; myocardial lactate) and oxidative stress (lipid hydroperoxides) were measured by enzyme-linked immunosorbent assay and Western blot. Myocardial matrix metalloproteinase-2 activity was quantified by gelatin zymography and immunoprecipitation. SETTING: University animal laboratory. SUBJECTS: Piglets (1-4 d old, weighing 1.4-2.5 kg). INTERVENTIONS: IV doxycycline (3, 10, or 30 mg/kg) given during resuscitation. MEASUREMENTS AND MAIN RESULTS: Hypoxic piglets had cardiogenic shock (cardiac output 58% ± 1% of baseline), hypotension (systemic arterial pressure 31 ± 1 mm Hg), and acidosis (pH 7.02 ± 0.02). Doxycycline improved cardiac and stroke volume index with no chronotropic effect in doxycycline-treated piglets compared with controls. Systemic arterial pressure was higher and the pulmonary artery pressure/systemic arterial pressure ratio was lower in doxycycline groups, with reduced levels of markers of myocardial injury and oxidative stress in doxycycline-treated piglets compared with controls. Negative correlations were found between markers of myocardial injury (plasma troponin I, myocardial lactate) and functional recovery and between myocardial tissue and plasma troponin I. Doxycycline-treated piglets had lower myocardial matrix metalloproteinase-2 activity compared with controls. CONCLUSIONS: Postresuscitation administration of doxycycline attenuates cardiac injury and improves functional recovery in newborn piglets with hypoxia-reoxygenation.

A novel ultrasensitive chemiluminescence enzyme immunoassay by employment of a signal enhancement of horseradish peroxidase-luminol-hydrogen peroxide reaction for the quantitation of atezolizumab, a monoclonal antibody used for cancer immunotherapy.

This study describes, for the first time, the development and validation of a novel ultrasensitive chemiluminescence enzyme immunoassay (CLEIA) for the quantification of atezolizumab (ATZ), a monoclonal antibody approved by the FDA for treatment of different types of cancer. The assay involved the non-competitive binding of ATZ to its specific antigen (PD-L1 protein). The immune complex of PD-L1/ATZ formed on the internal surface of the plate wells was quantified by a novel chemiluminescence (CL)-producing horseradish peroxidase (HRP) reaction. The reaction employed a highly efficient CL enhancer for the HRP-luminol-hydrogen peroxide reaction which was 4-(imidazol-1-yl)phenol. The conditions of the CLEIA and its detection system were refined, and the optimum procedures were established. The CLEIA was validated in accordance with the guidelines of immunoassay validation for bioanalysis, and all the validation criteria were acceptable. The assay's limit of detection and limit of quantitation were 12.5 and 37.5 pg mL-1, respectively, with a working dynamic range of 25-800 pg mL-1. The assay enables the accurate and precise quantitation of ATZ in human plasma samples without any interferences from endogenous substances and/or the plasma matrix. The results of the proposed CLEIA were favourably comparable with those of a pre-validated enzyme-linked immunosorbent assay using a colorimetric detection system. The CLEIA is characterized by simple and high throughput features. The CLEIA is superior to the existing analytical methodologies for ATZ. The proposed CLEIA has a great value in the quantitation of ATZ in clinical settings for assessment of its pharmacokinetics, therapeutic drug monitoring, and refining the safety profile.

Depression in patients with idiopathic pulmonary fibrosis.

Depression carries enormous global morbidity and is 1.5-7 times likelier to occur in individuals with chronic illness than in the general population. Idiopathic pulmonary fibrosis (IPF) has a rising incidence with a severe impact on quality of life. An indication of the prevalence of depression in this group is therefore of paramount interest. A prospective study was performed. A total of 118 participants with IPF who attended the interstitial lung disease clinic in Ninewells Hospitals, Dundee, Scotland, from May 2010 to September 2011 were recruited. Informed consent was obtained. The male to female ratio was 60:58. The Wakefield Self-assessment of Depression Inventory was used (scores ≥15 denote a depressed state). Pulmonary function tests were measured to correlate disease severity with depression scores. Of them, 58 patients had significant depressive symptoms scoring ≥15; only nine were taking antidepressant medication. The mean depression score of female participants was 15.0 ± 0.77 (SD 5.9), compared with a mean male score of 13.1 ± 0.99 (SD 7.5). Disease severity, age, duration since diagnosis and number of co-morbidities were not significantly correlated with depression. The study population had a high prevalence of depressive symptoms. Medical therapy for pulmonary fibrosis is limited and therefore palliation of symptoms and pulmonary rehabilitation form the main strategy for management. Depression should be actively screened in patients with IPF.

MMP-2 regulates Src activation via repression of the CHK/MATK tumor suppressor in osteosarcoma.

BACKGROUND: Doxorubicin, a first-line anticancer drug for osteosarcoma treatment, has been the subject of recent research exploring the mechanisms behind its chemoresistance and its ability to enhance cell migration at sublethal concentrations. Matrix metalloproteinase-2 (MMP-2), a type IV collagenase and zinc-dependent endopeptidase, is well-known for degrading the extracellular matrix and promoting cancer metastasis. Our previous work demonstrated that nuclear MMP-2 regulates ribosomal RNA transcription via histone clipping, thereby controlling gene expression. Additionally, MMP-2 activity is regulated by the non-receptor tyrosine kinase and oncogene, Src, which plays a crucial role in cell adhesion, invasion, and metastasis. Src kinase is primarily regulated by two endogenous inhibitors: C-terminal Src kinase (Csk) and Csk homologous kinase (CHK/MATK). AIM: In this study, we reveal that the MMP-2 gene acts as an upstream regulator of Src kinase activity by suppressing its endogenous inhibitor, CHK/MATK, in osteosarcoma cells. METHODS AND RESULTS: We show that enhanced osteosarcoma cell migration which is induced by sublethal concentrations of doxorubicin can be overcome by inactivating the MMP-2 gene or overexpressing CHK/MATK. Our findings highlight the MMP-2 gene as a promising additional target for combating cancer cell migration and metastasis. This is due to its role in suppressing on the gene and protein expression of the tumor suppressor CHK/MATK in osteosarcoma. CONCLUSION: By targeting the MMP-2 gene, we can potentially enhance the effectiveness of doxorubicin treatment and reduce chemoresistance in osteosarcoma.

Mechanisms of cytosolic targeting of matrix metalloproteinase-2.

Matrix metalloproteinase-2 (MMP-2) is best understood for its biological actions outside the cell. However, MMP-2 also localizes to intracellular compartments and the cytosol where it has several substrates, including troponin I (TnI). Despite a growing list of cytosolic substrates, we currently do not know the mechanism(s) that give rise to the equilibrium between intracellular and secreted MMP-2 moieties. Therefore, we explored how cells achieve the unique distribution of this protease. Our data show that endogenous MMP-2 targets inefficiently to the endoplasmic reticulum (ER) and shows significant amounts in the cytosol. Transfection of canonical MMP-2 essentially reproduces this targeting pattern, suggesting it is the quality of the MMP-2 signal sequence that predominantly determines MMP-2 targeting. However, we also found that human cardiomyocytes express an MMP-2 splice variant which entirely lacks the signal sequence. Like the fraction of ER-excluded, full-length MMP-2, this variant MMP-2 is restricted to the cytosol and specifically enhances TnI cleavage upon hypoxia-reoxygenation injury in cardiomyocytes. Together, our findings describe for the first time a set of mechanisms that cells utilize to equilibrate MMP-2 both in the extracellular milieu and intracellular, cytosolic locations. Our results also suggest approaches to specifically investigate the overlooked intracellular biology of MMP-2.

Calpain inhibitors exhibit matrix metalloproteinase-2 inhibitory activity.

Matrix metalloproteinase (MMP)-2 is a zinc-dependent endopeptidase which, alongside its known extracellular actions, plays fundamental roles in oxidative stress-induced injury to the heart. Intracellular cleavage targets of MMP-2 selectively mediating this injury include the sarcomeric proteins troponin I, myosin light chain-1 and titin; some of these are also targeted by calpains. In myocardial ischemia and reperfusion injury, inhibitors of MMP-2 and some calpain inhibitors were shown to improve the recovery of contractile function. We hypothesized that the protective effects of calpain inhibitors may be due in part to their ability to inhibit MMP-2. Four calpain inhibitors (calpain inhibitor III, ALLM, ALLN, and PD-150606) were tested for their ability to inhibit MMP-2 in comparison to the selective MMP inhibitor ONO-4817. At 100 µM, all calpain inhibitors, except ALLM, showed significant inhibition of MMP-2 gelatinolytic activity. When assessed by the troponin I proteolysis assay, both ALLN and PD-150606, but neither ALLM nor calpain inhibitor III (at 20 µM), significantly inhibited MMP-2 activity. Using a fluorogenic MMP substrate peptide OmniMMP in a kinetic assay the rank order of IC(50) values against MMP-2 were: PD-150606

Pulsed laser-induced photocatalytic reduction of greenhouse gas CO2 into methanol: A value-added hydrocarbon product over SiC.

CO(2) was converted into value-added hydrocarbons (methanol) by laser-induced photocatalytic reduction of CO(2) over commercially available silicon-carbide (SiC) granules as catalyst. The conversion of CO(2) was carried out in a glass reactor having quartz window and equipped with stirring system and was provided with continuous CO(2) flow at ambient conditions. Laser radiations of 355 nm, which were generated by third harmonics of Nd:YAG laser (1060 nm) were applied as an excitation source. The methanol yield as a function of irradiation time and catalysts dosage were monitored by the gas chromatographic analysis (GD-FID) of water samples collected at prescribed intervals. A specific GC column was used which separated hydrocarbons efficiently without any interference from water present in the sample. The study indicated that the commercially available SiC granular material is an excellent catalyst in laser-induced photocatalytic conversion of CO(2) into high value hydrocarbons.

Titin is a target of matrix metalloproteinase-2: implications in myocardial ischemia/reperfusion injury.

BACKGROUND: Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and, on activation in ischemia/reperfusion injury, proteolyzes specific myofilament proteins. Here we determine whether titin is an intracellular substrate for MMP-2 and if its degradation during ischemia/reperfusion contributes to cardiac contractile dysfunction. METHODS AND RESULTS: Immunohistochemistry and confocal microscopy in rat and human hearts showed discrete colocalization between MMP-2 and titin in the Z-disk region of titin and that MMP-2 is localized mainly to titin near the Z disk of the cardiac sarcomere. Both purified titin and titin in skinned cardiomyocytes were proteolyzed when incubated with MMP-2 in a concentration-dependent manner, and this was prevented by MMP inhibitors. Isolated rat hearts subjected to ischemia/reperfusion injury showed cleavage of titin in ventricular extracts by gel electrophoresis, which was confirmed by reduced titin immunostaining in tissue sections. Inhibition of MMP activity with ONO-4817 prevented ischemia/reperfusion-induced titin degradation and improved the recovery of myocardial contractile function. Titin degradation was also reduced in hearts from MMP-2 knockout mice subjected to ischemia/reperfusion in vivo compared with wild-type controls. CONCLUSION: MMP-2 localizes to titin at the Z-disk region of the cardiac sarcomere and contributes to titin degradation in myocardial ischemia/reperfusion injury.

Biopsied jaw lesions in Kuwait: a six-year retrospective analysis.

OBJECTIVES: The aim of this study was to determine the relative frequency of jaw lesions in Kuwait. MATERIALS AND METHODS: Biopsy records and microscopic sections of all jaw biopsies seen in the Department of Histopathology at Amiri Hospital, Kuwait, during the period January 2004 to December 2009 were reviewed. The biopsies were divided into three major groups: developmental/inflammatory/reactive lesions (group 1), cystic lesions (group 2), and tumors and tumor-like lesions (group 3). Groups 2 and 3 were subdivided into odontogenic and nonodontogenic. RESULTS: Three hundred and eighty-five cases were reviewed. Of the 385 cases, 115 (29.9%) were in group 1, 178 (46.2%) in group 2, and 92 (23.9%) in group 3. Overall, radicular cysts (n = 95; 24.7%) were the most common biopsied jaw lesions, followed by chronic apical periodontitis (n = 59; 15.3%), dentigerous cysts (n = 51; 13.2%), and keratocystic odontogenic tumors (n = 30; 7.8%). In group 1, chronic apical periodontitis was the most frequent lesion (n = 59; 51.3%). In group 2, odontogenic cysts (n = 166; 93.3%) were more frequent than nonodontogenic cysts (n = 12; 6.7%), and radicular cysts (n = 95; 53.4%) were the most frequent lesions in this group. Odontogenic tumors (n = 61; 66.3%) were more frequent than nonodontogenic tumors (n = 31; 33.7%) in group 3. Keratocystic odontogenic tumors (n = 30; 32.6%) were the most frequent type of lesion in this group, followed by ameloblastoma (n = 17; 18.5%). Only 3 malignant lesions were found in this study. CONCLUSIONS: Cystic and inflammatory lesions of the jaw are more common than tumors and tumor-like lesions of the jaw in Kuwait. The majority of inflammatory lesions that occurred in the jaw were related to periapical inflammation. Most cystic and tumorous jaw lesions were odontogenic in origin. Locally aggressive odontogenic tumors were relatively more common than nonaggressive ones. Malignant jaw tumors were relatively rare.