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Introduction: SARS-CoV2, first reported in December 2019 in Wuhan as COVID-19 causing respiratory illness, rapidly evolved into a pandemic owing to its very high infectivity. There is insufficient evidence about if and how smoking affects the risk of COVID-19 infection, and the reports on whether smoking increases or reduces the risk of respiratory infections, are contradictory. Therefore, the current study was designed to determine the effects of nicotine consumption on the infectivity of COVID-19. Methods: We performed in silico computer simulation-based study. The structures of SARS-CoV2spike ectodomain, and its receptor ACE2, were obtained from PDB. The structure of nicotine and its metabolites NNK and NNAL were obtained from the PubChem chemical database. After optimization, they were interacted using AutoDock 4.2, to see the effect of nicotine, NNK, or NNAL presence on the docking of viral spike protein to its receptor ACE2. Results: ACE2 vs spike protein interaction results were used as a control (ZDOCK score 1498.484, with four hydrogen bonds). The NNK+ACE2 vs spike protein docking formed 10 hydrogen bonds with the highest ZDOCK score of 1515.564. NNAL+ ACE2 vs spike protein interaction formed eleven hydrogen bonds with the ZDOCK score of 1499.371. Nicotine+ACE2 vs spike protein docking showed the lowest ZDOCK score of 1496.302 and formed 8 hydrogen bonds. Whereas, NNK+spike vs ACE2 interaction had a ZDOCK score of 1498.490 and formed eight hydrogen bonds. NNAL+spike vs ACE2 docking formed eleven hydrogen bonds with a ZDOCK score of 1498.482. And Nicotine+spike vs ACE2 interaction showed a ZDOCK score of 1498.488 and formed 9 hydrogen bonds. Conclusions: The binding of nicotine to either spike of virus or its receptor ACE2 is not affecting the viral docking with the receptor. But binding of NNK, a metabolite of nicotine, is facilitating the viral docking with its receptor indicating that smoking may increase the risk of COVID-19 infection.

Introduction: Advanced glycation end-products (AGEs) are contributing factors to diabetes complications. The antigenic nature of AGEs established the theory of incessant accumulation of AGEs can incite an autoimmune response in a diabetic patient. Glycating agents like 3-deoxyglucosone are increased in diabetic patients, leading to the high formation of AGEs aggravating the pathophysiological conditions in diabetes. We aimed to study the immunogenicity of glycated histone H1 protein and AGEs (N-carboxymethyl-lysine and pentosidine) as well as detection of autoantibodies in the sera of type 2 diabetic subjects. Materials and Methods: Female rabbits were injected with native H1 and glycated-H1 to discern its immunogenicity. Diabetic subjects’ sera were also scanned for the detection of autoantibodies against glycated-H1 and AGEs using immunochemical assay technique. Results: Glycated-H1 was highly immunogenic, unlike the native analog. Diabetic sera showed 48% (72 of 150 samples) significantly strong binding with glycated-H1, further sera also showed 40% (60 of 150 samples), and 36% (54 of 150 samples) strong binding with CML, and pentosidine, respectively. Conclusion: The findings support modified H1 as well AGEs are highly immunogenic in nature. The presence of autoantibodies against glycated-H1 and AGEs may be utilized in the assessment of diabetes or its complications. Keywords: immunogenicity, 3-deoxyglucosone, advanced glycation end-products, diabetes

Arrangement of the content material of regional regulation as part of the legislations sub-system adjustment in Indonesia must be directed in tone with the direction of national law development. In accordance with the National Long-Term Development Plan (RPJPN, 2005-2025), the development of national law is directed at the realization of a solid national legal system based on the Pancasila and the 1945 Constitution of the Republic of Indonesia which includes the development of legal material, legal structures, legal culture legal apparatus, legal facilities and infrastructure that can guarantee order, legal certainty, justice, truth and protection of human rights. The discussion in this article aims to raise a number of important relevant issues to be used as material for evaluation in structuring the content of the regional regulations as a sub-system of national law. The research method used in this study is legal research using a legislative approach and a conceptual approach. It is concluded that the regulation of the content material of the regional regulation as a sub-system of national law is not only placed in the legal sense as a mere system of order, thus creating a relationship of tension between the central government and the regional government, it but must be placed in a legal sense as a fluid relationship so that the determination of the content of the regional regulation is also fluid, for the good of the community and the government as a whole.

Methylglyoxal (MG) is a reactive dicarbonyl intermediate and a precursor of advanced glycation end products (AGEs). The authors investigated the role played by AGEs in muscle myopathy and the amelioration of its effects by curcumin and gingerol. In addition to producing phenotypical changes, MG increased oxidative stress and reduced myotube formation in C2C12 cells. RAGE (receptor for AGEs) expression was up-regulated and MYOD and myogenin (MYOG) expressions were concomitantly down-regulated in MG-treated cells. Interestingly, AGE levels were higher in plasma (~32 fold) and muscle (~26 fold) of diabetic mice than in control mice. RAGE knock-down (RAGEkd) reduced the expressions of MYOD and MYOG and myotube formation in C2C12 cells. In silico studies of interactions between curcumin or gingerol and myostatin (MSTN; an inhibitor of myogenesis) and their observed affinities for activin receptor type IIB (ACVRIIB) suggested curcumin and gingerol reduce the interaction between MSTN and ACVRIIB. The findings of this study suggest enhanced AGE production and subsequent RAGE-AGE interaction obstruct the muscle development program, and that curcumin and gingerol attenuate the effect of AGEs on myoblasts.

Advanced glycation end-products comprise a complex and heterogeneous group of compounds that have been implicated in diabetes-related complications. The importance of the Maillard reaction is depicted by the formation of reactive intermediate products known as α-oxoaldehydes, such as 3-deoxyglucosone (3-DG). This product has been found to be involved in accelerated vascular damage in diabetes. In the present study, calf thymus histone H2A was reacted with 3-DG, and the generation of advanced glycation end products was investigated by determining the degree of side chain modifications (lysine and arginine residues), Amadori products, carbonyl content, Ne-carboxymethyl lysine, and pentosidine using various physicochemical techniques. Moreover, fluorescence, absorbance as well as structural characteristics of glycated-H2A were comprehensively investigated. Overall, this study demonstrates structural perturbation, formation of different intermediates, and AGEs that are believed to hamper the normal functioning of H2A histone, compromising the integrity of chromatin structures and function in secondary complications of diabetes. © 2014 IUBMB Life, 66(10):686–693, 2014

Peroxynitrite is a bifaceted reactive species. It can oxidize and nitrate proteins/nucleic acids/lipids and is involved in inflammation, apoptosis, cytotoxicity and autoimmune disorders of unknown etiology, including SLE. In this study, H3 histone exposed to peroxynitrite caused loss of tertiary structure, nitration of tyrosine residues and dityrosine formation. Experimentally produced antibodies against peroxynitrite-modified H3 histone showed specificity for the immunogen. However, cross-reactions with other nitrated proteins were also observed. We further investigated the binding of SLE autoantibodies with native DNA, native H3 histone and peroxynitrite-modified H3 histone to explore the possible role of modified-H3 histone in the initiation and/or progression of SLE in a sub-group of patients. The results showed preferential binding of SLE anti-nDNA autoantibodies to peroxynitrite-modified H3 histone. The visual detection of immune complex formation with native and peroxynitrite-modified H3 histone reiterated preferential binding of SLE autoantibodies with modified H3 histone. It may be concluded that anti-histone autoantibodies seen in a subgroup of SLE patients might be due to the immunogenicity of peroxynitrite-modified H3 histone.

The available data suggest that among cellular constituents, proteins are the major target for oxidation primarily because of their quantity and high rate of interactions with ROS. Proteins are susceptible to ROS modifications of amino acid side chains which alter protein structure. Among the amino acids, Cysteine (Cys) is more prone to oxidation by ROS because of its high nucleophilic property. The reactivity of Cys with ROS is due to the presence of thiol group. In the oxidised form, Cys forms disulfide bond, which are primary covalent cross-link found in proteins, and which stabilize the native conformation of a protein. Indirect evidence suggests that thiol modifications by ROS may be involved in neurodegenerative disorders, but the significance and precise extent of the contributions are poorly understood. Here, we review the role of oxidized Cys in different pathological consequences and its biochemistry may increase the research in the discovery of new therapies. The purpose of this review is to re-examine the role and biochemistry of oxidised Cys residues.

Advanced glycation end-products (AGEs) resulting from non-enzymatic glycation are one of the major factors implicated in secondary complications of diabetes. Scientists are focusing on discovering new compounds that may be used as potential AGEs inhibitors without affecting the normal structure and function of biomolecules. A number of natural and synthetic compounds have been proposed as AGE inhibitors. In this study, we investigated the inhibitory effects of AgNPs (silver nanoparticles) in AGEs formation. AgNPs (~30.5 nm) synthesized from Aloe Vera leaf extract were characterized using UV-Vis spectroscopy, energy-dispersive X-ray spectroscopy (EDX), high resolution-transmission electron microscopy, X-ray diffraction and dynamic light scattering (DLS) techniques. The inhibitory effects of AgNPs on AGEs formation were evaluated by investigating the degree of reactivity of free amino groups (lysine and arginine residues), protein-bound carbonyl and carboxymethyl lysine (CML) content and the effects on protein structure using various physicochemical techniques. The results showed that AgNPs significantly inhibit AGEs formation in a concentration dependent manner and that AgNPs have a positive effect on protein structure. These findings strongly suggest that AgNPs may play a therapeutic role in diabetes-related complications.

Osteoarthritis (OA) is characterized by inflammation of the knee joint, which is caused by accumulation of cytokines and C-reactive protein (CRP) in the extracellular matrix as an early immune response to infection. The articular cartilage destruction is discernible by elevated tumour necrosis factor-α (TNF-α). In this study, blood samples of knee osteoarthritis patients were analyzed for biochemical and physiological parameters based on the lipid profile, uric acid, total leukocyte count (TLC), hemoglobin percentage (Hb%) and absolute lymphocyte count (ALC). Furthermore, immunological parameters including TNF-α , interleukin-6 (IL-6) and CRP were analyzed. The presence of antibodies against hydroxyl radical modified collagen-II (•OH-collagen-II) was also investigated in arthritis patients using direct binding ELISA. The uric acid and lipid profiles changed extensively. Specifically, increased uric acid levels were associated with OA in both genders, as were enhanced immunological parameters. The TNF-α level also increased in both genders suffering from OA. Finally, auto-antibodies against OH-collagen II antigen were found in the sera of arthritis patients. These results indicated that immunological parameters are better predictors or indexes for diagnosis of OA than biochemical parameters., EXCLI Journal; 14:Doc1057; ISSN 1611-2156

Advanced glycation end products (AGEs) culminate from the non-enzymatic reaction between a free carbonyl group of a reducing sugar and free amino group of proteins. 3-deoxyglucosone (3-DG) is one of the dicarbonyl species that rapidly forms several protein-AGE complexes that are believed to be involved in the pathogenesis of several diseases, particularly diabetic complications. In this study, the generation of AGEs (N-epsilon-carboxymethyl lysine and pentosidine) by 3-DG in H1 histone protein was characterized by evaluating extent of side chain modification (lysine and arginine) and formation of Amadori products as well as carbonyl contents using several physicochemical techniques. Results strongly suggested that 3-DG is a potent glycating agent that forms various intermediates and AGEs during glycation reactions and affects the secondary structure of the H1 protein. Structural changes and AGE formation may influence the function of H1 histone and compromise chromatin structures in cases of secondary diabetic complications.

Advanced glycation end-products (AGEs) are heterogeneous group of compounds, known to be implicated in diabetic complications. One of the consequences of the Maillard reaction is attributed to the production of reactive intermediate products such as a-oxoaldehydes. 3deoxyglucosone (3-DG), an alpha-oxoaldehyde has been found to be involved in accelerating vascular damage during diabetes. In the present study, calf thymus histone H3 was treated with 3-deoxyglucosone to investigate the generation of AGEs (N-epsilon-carboxymethyllysine, pentosidine), by examining the degree of side chain modifications and formation of different intermediates and employing various physicochemical techniques. The results clearly indicate the formation of AGEs and structural changes upon glycation of H3 by 3-deoxyglucosone, which may hamper the normal functioning of H3 histone, that may compromise the veracity of chromatin structures and function in secondary complications of diabetes.

Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively.

Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC) and other oral lesions. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied Photodynamic therapy (PDT) efficacy depends on the local dose deposited in the lesion as well as oxygen availability in the lesion. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry.

Optimasi produksi enzim lipase dari isolate Aspergillus oryzae pada kopra berjamur telah dilakukan. Isolasi enzim dilakukan setelah fungi tersebut diaktifkan dan dikultur pada media yang mengandung pepton dan minyak zaitun pada suhu 370C dan pH 7,0 selama 8 hari. Optimasi produksi enzim lipase dilakukan dengan memvariasikan komposisi media produksi yaitu: konsentrasi pepton dan minyak zaitun serta kecepatan pengadukan optimum. Hasil penelitian menunjukkan bahwa aktivitas enzim lipase tertinggi diperoleh pada konsentrasi pepton 1%, konsentrasi minyak zaitun 3% dan kecepatan pengadukan 150 rpm. Dari optimasi konsentrasi media produksi dan kecepatan pengadukan diperoleh bahwa ada kenaikan aktivitas enzim lipase dari 13.222 U/mLmenjadi 18.888 U/mL.

Penelitian ini menggunakan isolat fungi Aspergillus oryzae dari kopra ber-jamur sebagai sumber enzim lipase. Isolasi enzim dilakukan setelah fungi tersebut diaktifkan dan dikultur pada masing-masing media fermentasi yang mengandung substrat olive oil, virgin oil, triolein dan palm oil pada suhu 370C dan pH 7,0 selama 8 hari. Enzim lipase yang dihasilkan dilakukan uji aktivitas, dan dari uji aktivitas didapatkan bahwa enzim lipase dapat menghidrolisis semua substrat, dan aktivitas paling tinggi diperoleh pada substrat triolein. Uji aktivitas dilakukan dengan menam-bahkan ion-ion logam yaitu: Co2+, Ca2+, Mg2+, Ni2+, Mn2+, Zn2+ dan EDTA, dengan konsentrasi masing-masing 1mM dan 10 mM. Dari hasil penelitian diperoleh ion-ion Co2+, Ca2+ dan Mg2+ dapat meningkatkan aktivitas enzim sebesar masing-masing Co2+ = 19% dan 6%, Ca2+ = 4% dan 8% pada konsentrasi 1mM dan 10 mM, Mg2+ tidak meningkatkan aktivitas enzim pada konsentrasi 1mM, tetapi pada konsentrasi 10 mM meningkatkan aktivitas enzim 11%. Ion Ni2+, Mn2+ dan Zn2+ tidak meningkatkan aktivitas enzim, demikian pula dengan penambahan EDTA.

Suatu kalkon telah diisolasi dari kulit batang Cryptocarya costata. Isolat diperoleh dari fraksi kloroform, setelah fraksinasi dengan teknik kromatografi yang dilanjutkan dengan rekristalisasi dalam heksana dan etilasetat, dihasilkan kristal jarum berwarna kuning dengan titik leleh 167-169oC. Elusidasi struktur isolat berdasarkan spektrum UV, IR, 1 D dan 2D NMR, maka dapat ditetapkan bahwa senyawa isolat adalah 2’,4’-Dihidroksi-3’,6’-dimetoksicalkon. Uji sitotoksik terhadap E.coli, menunjukkan aktivitas positif dengan nilai hambat 35,4 %, dan pertama kali ditemukan dari tumbuhan Cryptocarya Kata kunci : Kalkon, Sitotoksik, Cryptocarya costata

Three species of bacteria, 8 species of fungi and 3 species of VAM-fungi were isolated from the soil substrata supporting Avicennia marina which comprises the majority of mangrove vegetation along the Karachi coast. The species abundances for fungi and bacteria were greater at one site (Sandspit) supporting healthy mangrove growth with soil pH 7.8, EC 16.2mmhos/cm², TSS 2.57% and available phosphorus 0.008% than at the other site (Korangi creek) with stunted growth of mangrove where the soil samples showed pH 7.9, EC 18.8mmhos/cm², TSS 1.45% and available phosphorus 0.001%. Symbiotic association by vasicular-arbuscular mycorrhizal (VAM) fungi in the roots of mangrove plants was also observed on a small scale at Korangi creek where the substratum was undergoing microbial degradation.