Acceleration of protein glycation by oxidative stress and comparative role of antioxidant and protein glycation inhibitor.

Hyperglycemia in diabetes causes protein glycation that leads to oxidative stress, release of cytokines, and establishment of secondary complications such as neuropathy, retinopathy, and nephropathy. Several other metabolic disorders, stress, and inflammation generate free radicals and oxidative stress. It is essential to study whether oxidative stress independently enhances protein glycation leading to rapid establishment of secondary complications. Oxidative stress was experimentally induced using rotenone and Fenton reagent for in vivo and in vitro studies, respectively. Results showed significant increase in the rate of modification of BSA in the form of fructosamine and protein-bound carbonyls in the presence of fenton reagent. Circular dichroism studies revealed gross structural changes in the reduction of alpha helix structure and decreased protein surface charge was confirmed by zeta potential studies. Use of rotenone demonstrated enhanced AGE formation, ROS generation, and liver and kidney tissue glycation through fluorescence measurement. Similar findings were also observed in cell culture studies. Use of aminoguanidine, a protein glycation inhibitor, demonstrated reduction in these changes; however, a combination of aminoguanidine along with vitamin E demonstrated better amelioration. Thus, oxidative stress accelerates the process of protein glycation causing gross structural changes and tissue glycation in insulin-independent tissues. Use of antioxidants and protein glycation inhibitors in combination are more effective in preventing such changes and could be an effective therapeutic option for preventing establishment of secondary complications of diabetes.

Hierarchical Self-Assembly of Supramolecular Coordination Polymers Using Giant Metal-Organic Nanocapsules as Building Blocks.

Controlling the self-assembly of giant molecular building blocks into complex architectures with similar hierarchy to biological species remains a major challenge in supramolecular chemistry. Akin to protein structure, here we present the self-assembly of giant molecular nanocapsules into supramolecular coordination polymers with controlled hierarchy from primary to secondary and tertiary structures. First, we successfully prepared discrete nanocapsules (secondary structures) consisting of multicomponents, such as organic macrocycles and metal-based secondary building units (primary structures). Second, these nanocapsules can self-organize into various 2D and 3D supramolecular coordination polymers (tertiary structures) through coordination-driven assembly. The periphery 24 flexible alkyl chains and 24 metal ions available for potential coordination make these nanocapsules comparable to functionalized solid nanoparticles with non-specific binding sites at the surface and allow the nanocapsules to self-adjust their orientations and coordination modes to facilitate the self-assembly process. This study sheds light on the self-assembly of giant building units with complex molecular structures and opens up possibilities for the design of new hierarchical architectures with innovative properties and functions in many applications such as biomimics, biomedicine, and molecular devices.

Formation of Water Channels in the Crystalline Hydrates of Macrocyclic Compounds.

Crystalline hydrates of macrocyclic compounds such as pyroagllol[4]arenes (PgCs) and resorcin[4]arenes (RsCs) are rare owing to their lower water solubility. Functionalization of these macrocyclic compounds is an affordable way to enhance water solubility. However, functionalization also encounters the formation of multiple conformers and subsequent difficulty in purification of the product. Herein, four novel crystalline hydrates of functionalized PgCs and RsCs were synthesized. Formation of water channels and the effects of intermolecular interactions on the physical properties of these novel hydrates are discussed.

Synthesis of Protected Amino Hexitol Nucleosides as Building Blocks for Oligonucleotide Synthesis.

A new synthesis protocol for the preparation of hitherto unknown 1',5'-anhydro-4'-amino-trityl/MMTr hexitol nucleosides has been developed. Key steps in the synthesis of the pyrimidine analogues (U and C) include the regioselective d- allo-hexitol oxirane and 2',4'-anhydronucleoside ring opening by uracil and azide, respectively. A different strategy using a regioselective epoxide ring opening of d- gulo-oxirane, followed by a SN2 type of azidation reaction, has been adopted for the purine analogues (A and G). These compounds can be easily converted to 6'-phosphoramidites for the solid-phase synthesis of N4' → P6' phosphoramidates of amino hexitol nucleic acids (AHNA).

Controlled 2D Assembly of Nickel-Seamed Hexameric Pyrogallol[4]arene Nanocapsules.

The two-dimensional framework of nickel-seamed hexameric metal-organic nanocapsules has been synthesized by connecting the tailed hydroxyl groups of C-propan-3-ol pyrogallol[4]arene with adjacent hexameric capsules via nickel-hydroxyl coordination. In addition, functionalization of nanocapsules with multiple pyridine molecules at the capsule surface prevents them from assembling into hierarchical structures and leads to the formation of discrete nickel-seamed pyrogallol[4]arene nanocapsules. This work shows that surface functionalization of nanocapsules is an effective and innovative method of controlling the assembly of these nanometric building blocks.

Preparation of Magnesium-Seamed C-Alkylpyrogallol[4]arene Nanocapsules with Varying Chain Lengths.

Novel supramolecular nanocapsules based on metal-directed assembly have captured tremendous interest due to their applications in fields such as catalysis, selective gas adsorption, and biomedicine. Functionalization of metal-organic nanocapsules (MONCs) by using organic ligands with different pendant groups affords more complexity to the structure and may lead to novel properties. In this work, we report the solvothermal synthesis of a group of magnesium-based MONCs using C-alkylpyrogallol[4]arenes with varying alkyl chain lengths. The structures of these nanocapsules are characterized by single-crystal X-ray diffraction analysis. As expected, a progression in size of the nanocapsules is observed as the alkyl chain length increases. The effect of the chain length on the solubility of MONCs in water has been determined. This work shows the generality of the solvothermal approach for the synthesis of MONCs with different organic ligands and demonstrates that surface functionalization of MONCs may serve as an effective way to tailor their properties. The unique biocompatible nature and inherent large cavity of these magnesium-based MONCs make these nanocapsules promising for potential applications in biomedicine.

Cadiolides J-M, antibacterial polyphenyl butenolides from the Korean tunicate Pseudodistoma antinboja.

Activity-guided fractionations of the tunicate Pseudodistoma antinboja yielded four new compounds of the cadiolide class (cadiolides J-M, 1, 3-5) along with a known one (cadiolide H, 2). The structures were defined by spectroscopic methods including X-ray crystallographic analysis. These compounds were evaluated for their antibacterial activity and exhibited potent antibacterial activity against all of the drug resistant strains tested with MICs comparable to those of marketed drugs such as vancomycin and linezolid.

Process Development for Separation of Conformers from Derivatives of Resorcin[4]arenes and Pyrogallol[4]arenes.

Macrocyclic compounds, such as resorcin[4]arenes and pyrogallol[4]arenes, have proven to be useful building blocks in the construction of supramolecular organic frameworks (SOFs) because of their unique bowl-like shape and ability to interact through variety of intermolecular interactions. Herein, we report the synthesis and crystal structures of two functionalized resorcin[4]arenes and pyroagllol[4]arenes, 4-hydroxyphenylresorcin[4]arenes, and 4-hydroxyphenylpyrogallol[4]arenes. These phenyl-functionalized macrocycles usually have different conformers, such as cone, boat, chair, saddle, and diamond. The successful separation of predominant conformers from the crude product was carried out with solvent-extraction technique. The shape and molecular arrangement of these conformers in the individual crystal structure was verified with single-crystal X-ray diffraction studies.

Noria: A Highly Xe-Selective Nanoporous Organic Solid.

Separation of xenon and krypton is of industrial and environmental concern; the existing technologies use cryogenic distillation. Thus, a cost-effective, alternative technology for the separation of Xe and Kr and their capture from air is of significant importance. Herein, we report the selective Xe uptake in a crystalline porous organic oligomeric molecule, noria, and its structural analogue, PgC-noria, under ambient conditions. The selectivity of noria towards Xe arises from its tailored pore size and small cavities, which allows a directed non-bonding interaction of Xe atoms with a large number of carbon atoms of the noria molecular wheel in a confined space.

Selective CO2 Adsorption in a Supramolecular Organic Framework.

Considering the rapidly rising CO2 level, there is a constant need for versatile materials which can selectively adsorb CO2 at low cost. The quest for efficient sorptive materials is still on since the practical applications of conventional porous materials possess certain limitations. In that context, we designed, synthesized, and characterized two novel supramolecular organic frameworks based on C-pentylpyrogallol[4]arene (PgC5 ) with spacer molecules, such as 4,4'-bipyridine (bpy). Highly optimized and symmetric intermolecular hydrogen-bonding interactions between the main building blocks and comparatively weak van der Waals interactions between solvent molecules and PgC5 leads to the formation of robust extended frameworks, which withstand solvent evacuation from the crystal lattice. The evacuated framework shows excellent affinity for carbon dioxide over nitrogen and adsorbs ca. 3 wt % of CO2 at ambient temperature and pressure.

Anion- and Spacer-Directed Host-Guest Complexes of Bipyridine with Pyrogallol[4]arene.

New oval-shaped capsular and bilayer-type hydrogen-bonded arrangements of C-propyl-ol-pyrogallol[4]arene (PgC3-OH) with bipyridine-type spacer complexes are reported here. These complexes are engineered by virtue of derivatization of C-alkyl tails of pyrogallol[4]arene and the use of divergent spacer ligands. Complexes of PgC3-OH, PgC3-OH with bpy (4,4'-bipyridine) and PgC3-OH with bpa (1,2-bis(4-pyridyl)acetylene) have bilayer type arrangements; however, the use of hydrogen chloride causes protonation of bpy molecule, which is then entrapped flat within an offset oval-shaped dimeric hydrogen-bonded PgC3-OH nanocapsule. The presence of chloride anion in the crystal lattice controls the geometry of the resultant nanoassembly.

Monanchosterols A and B, bioactive bicyclo[4.3.1]steroids from a Korean sponge Monanchora sp.

Chemical investigation of a Korean marine sponge, Monanchora sp., led to the isolation of three new steroids (1-3). Compounds 1 and 2, designated as monanchosterols A and B, respectively, represent the first examples of steroids possessing the bicyclo[4.3.1] A/B ring system from a natural source. Compounds 1-3 were investigated for their anti-inflammatory activity by evaluating their inhibitory effects on the mRNA expression of IL-6, TNF-α, and COX-2 in the LPS-stimulated murine RAW264.7 macrophage cells. Compounds 2 and 3 exhibited significant inhibitory effects on the mRNA expression of IL-6 without notable cytotoxicity to the cells in a dose-dependent manner.

Anithiactins A-C, modified 2-phenylthiazoles from a mudflat-derived Streptomyces sp.

Intensive investigation of the chemical components of a Streptomyces sp. isolated from mudflat sediments collected on the southern coast of the Korean peninsula led to the isolation of three new compounds, anithiactins A-C (1-3). The chemical structures of anithiactins A and C were determined by interpretation of NMR data analyses, while the chemical structure of anithiactin B was established from a combination of NMR spectroscopic and crystallographic data analyses. The structure of anithiactin A was also confirmed by total synthesis. These three anithiactins displayed moderate acetylcholinesterase inhibitory activity with no significant cytotoxicity.

A Case Report of Simultaneous Intracranial Hemorrhage and Cerebral Venous Sinus Thrombosis in a Young Indian Male: Diagnostic and Therapeutic Challenges.

This case report discusses the intricate diagnostic and therapeutic challenges faced by a 23-year-old Indian male who presented with altered consciousness, a holo-cranial headache, right-sided hemiparesis, and subsequent neurological symptoms. The patient's dietary habits, leading to vitamin B12 and folic acid deficiencies resulting in hyperhomocysteinemia, along with binge alcohol drinking leading to dehydration, were identified as the main causes of cerebral venous sinus thrombosis (CVST) in this case. The case was complicated by an additional cerebral hemorrhage. The patient received a comprehensive treatment regimen involving antiepileptic medications, intravenous fluids, and anticoagulation therapy. A decline in the Glasgow Coma Scale score prompted further interventions. Collaborative decision-making, involving neurologists, neurosurgeons, and the patient's relatives, steered the treatment course, ultimately favoring continued medical management over decompression surgery. Notably, the patient exhibited remarkable progress in mobility, achieving the ability to walk with support by the end. This case report contributes valuable insights to the understanding of CVST, emphasizing the significance of nutritional considerations, especially in vegetarians, and underscoring the importance of thorough diagnostic evaluations in complex clinical scenarios.

Exploring the glycation association with dyslipidaemia: Novel approach for diabetic nephropathy.

The transcription factor known as sterol regulatory element-binding protein (SREBP) and the glycation pathways, specifically the formation of Advanced Glycation End Products (AGEs), have a significant and deleterious impact on the kidney. They alter renal lipid metabolism and promote glomerulosclerosis, mesangial cell expansion, tubulointerstitial fibrosis, and inflammation, leading to diabetic nephropathy (DN) progression. Although several pieces of scientific evidence are reported for potential causes of glycation and lipotoxicity in DN, the underlying mechanism of renal lipid accumulation still needs to be fully understood. We provide a rationalized view on how AGEs exert multiple effects that cause SREBP activation and inflammation, contributing to DN through Receptor for AGEs (RAGE) signaling, AGE-R1-dependent downregulation of Sirtuin 1 (SIRT-1), and increased SREBP Cleavage Activating Protein (SCAP) glycosylation. This review emphasizes the association between glycation and the SREBP pathway and how it affects the onset of DN associated with obesity. Finally, we discuss the correlation of glycation and the SREBP pathway with insulin resistance (IR), oxidative stress, endoplasmic reticulum stress, inflammation, and existing and emerging therapeutic approaches toward better controlling obesity-related DN.

A Study on the Etiology and Clinical Manifestations of Community-Acquired Pneumonia in Adults in Western India.

BACKGROUND:  Community-acquired pneumonia (CAP) is an acute lung infection affecting the alveoli in individuals who have not had recent exposure to healthcare settings. It is characterized by newly detected pulmonary infiltration on a chest X-ray or computed tomography scan, accompanied by at least two of the following symptoms: a new or worsening cough, shortness of breath, increased sputum production, fever or hypothermia, pleuritic chest pain, hypoxia, confusion, or an abnormal WBC count (either leukopenia or leukocytosis). It is a major contributor to global mortality and morbidity, especially in elderly populations. This study aims to investigate the etiology of CAP in our region and analyze the clinical characteristics of patients diagnosed with CAP. METHODOLOGY:  This prospective, hospital-based study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, a 2,011-bed multispecialty hospital. The study included 100 patients over 18 years old, diagnosed with CAP, and hospitalized between January 2023 and January 2024. All patients underwent a thorough clinical assessment, and sputum cultures were collected on the day of admission. Patients under 18 years old, those who had been hospitalized within the preceding two weeks, individuals with pneumonia caused by tuberculosis or aspiration pneumonia, patients with compromised immune systems, and pregnant women were excluded. RESULTS:  The study included 100 patients with a mean age of 53.13 years (±18.31). The most common age group was 59-68 years, which included 25 (25%) cases, followed by the 69-78 year age group with 18 (18%) cases and the 18-28 year age group with 15 (15%) cases. The majority were male, with 61 (61%) cases. Common symptoms included fever in 78 cases (78%), chest pain in 69 cases (69%), dyspnea in 65 cases (65%), and cough in 51 cases (51%). Sputum cultures showed growth in 65 cases (65%), with Klebsiella pneumoniae being the most prevalent pathogen in 28 cases (43%), followed by Streptococcus pneumoniae in 18 cases (28%). Together, these two pathogens accounted for 46 out of 65 positive samples (70%). CONCLUSIONS:  This study highlights the clinical profile and rising etiology of K. pneumoniae in CAP in adults in Western India, particularly in the elderly. These findings underscore the need for periodic updates on CAP etiology to inform empirical treatment strategies effectively. Future research should use advanced diagnostics and diverse samples to refine CAP management, with continuous monitoring to update treatment protocols.

A Systematic Review of Community-Acquired Pneumonia in Indian Adults.

This systematic review aimed to consolidate findings on the etiology of community-acquired pneumonia (CAP) among Indian adults. We adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Guidelines 2020 and conducted a comprehensive search across databases including PubMed, Scopus-Elsevier, and hand-searched reference lists using key terms such as "Community-Acquired Pneumonia," "CAP," "Indian," and "adults." Articles published between January 2010 and January 2024 were included, with exclusions for studies involving pediatric populations, non-Indian patients, or those published before 2010. From an initial pool of 344 articles, duplicates were removed and titles and abstracts were screened, resulting in nine studies meeting the inclusion criteria. The analysis of pooled data comprising 1,643 Indian adult participants revealed the following pathogen distribution: Streptococcus pneumoniae was the most common organism, accounting for 33% of the cases. This was followed by Klebsiella pneumoniae at 23%, Staphylococcus aureus at 10%, Mycoplasma pneumoniae and Legionella pneumophila each at 7%, and Chlamydia pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa each at 4%. Notably, the review highlights a rising incidence of K. pneumoniae in CAP cases, which is a significant concern and should be considered when treating CAP patients in India. The findings emphasize the importance of comprehensive diagnostic testing, including advanced methods such as bronchoalveolar lavage, urinary antigen tests, serology for atypical pathogens, and enzyme-linked immunosorbent assays, to improve diagnostic yield and guide targeted antibiotic therapy. This review underscores the need for updated empirical treatment guidelines that account for dominant pathogens. Future research should focus on employing advanced diagnostic methods to enhance understanding of CAP etiology.

A Study of Abnormal Echocardiogram Findings in Patients With Chronic Kidney Disease With Reference to Cardiac Biomarkers.

Background Chronic kidney disease (CKD) is prevalent, especially in populations with multiple risk factors, such as undiagnosed and untreated hypertension and diabetes mellitus. Cardiovascular diseases (CVDs) leading to poor quality of life or even death have been noted as an increasing trend among CKD patients. This study aims to use cardiac biomarkers to evaluate their association with abnormal echocardiogram findings in CKD patients, which may allow for the improvement of quality of life with early treatment. Methods and materials This observational, cross-sectional study was conducted on 103 diagnosed CKD patients at the Department of Medicine, Dr. D.Y. Patil Medical College, Hospital, and Research Centre in Pimpri, Pune, from January 2023 to January 2024. Ethical approval was acquired, and written consent was obtained from participants. The study utilised cardiac biomarkers such as N-terminal pro-B type natriuretic peptide (NT-proBNP), troponin I (Trop I), and a radiological tool, transthoracic echocardiography (TTE). All patients with diagnosed stages 3, 4, and 5 CKD between the ages of 18-80 years were included, and the exclusion criteria consisted of patients who had already undergone cardiac interventional procedures or known cases of CVDs. Results In our study, out of 103 participants, the majority were aged between 51 and 60 years (35, 34%). The study had a majority of male participants (76, 73.8%). Major risk factors were considered, noting hypertension in 63 (61.2%) and diabetes mellitus in 81 (78.6%). Participants were divided into stages of CKD. Cardiac biomarkers such as NT-proBNP and Trop I levels were assessed in all participants in the different stages of CKD showing elevated levels of NT-proBNP across all stages. Transthoracic echocardiogram (TTE) screening tests were also evaluated for all patients, showing diastolic dysfunction (DD) as the most common finding in stage 3 (5, 41.67%), stage 4 (25, 62.5%), and stage 5 (35, 68.83%), followed by left ventricular hypertrophy (LVH) as a common finding in stage 3 (4, 33.3%), stage 4 (20, 50%), and stage 5 (30, 58.2%) CKD. Furthermore, the association between raised cardiac biomarkers and abnormal echocardiogram findings across the stages of CKD was evaluated, resulting in a statistically significant association with p-values < 0.05. Conclusion This research sheds light on the association between cardiac biomarkers and abnormal echocardiogram findings in CKD patients and helps us determine if there is any added benefit or predictive value in screening these individuals at different stages of the disease to allow early intervention and improvement in treatment and quality of life.

Extracellular purines in lung endothelial permeability and pulmonary diseases.

The purinergic signaling system is an evolutionarily conserved and critical regulatory circuit that maintains homeostatic balance across various organ systems and cell types by providing compensatory responses to diverse pathologies. Despite cardiovascular diseases taking a leading position in human morbidity and mortality worldwide, pulmonary diseases represent significant health concerns as well. The endothelium of both pulmonary and systemic circulation (bronchial vessels) plays a pivotal role in maintaining lung tissue homeostasis by providing an active barrier and modulating adhesion and infiltration of inflammatory cells. However, investigations into purinergic regulation of lung endothelium have remained limited, despite widespread recognition of the role of extracellular nucleotides and adenosine in hypoxic, inflammatory, and immune responses within the pulmonary microenvironment. In this review, we provide an overview of the basic aspects of purinergic signaling in vascular endothelium and highlight recent studies focusing on pulmonary microvascular endothelial cells and endothelial cells from the pulmonary artery vasa vasorum. Through this compilation of research findings, we aim to shed light on the emerging insights into the purinergic modulation of pulmonary endothelial function and its implications for lung health and disease.

Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and, as such, provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may result in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in epigenetic regulation primarily by modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extranuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases, and we will discuss the potential of their inhibitors for lung injury prevention.