Recent Advances in Biomedical Applications of Biogenic Nanomaterials.

The synthesis of biogenic nanoparticles from readily available natural resources may have large demand in numerous fields including pharmaceuticals and medicine. The biogenic nanoparticles catch the attention of the scientific community due to their low cytotoxicity and biocompatibility. Chemical, physical, and greener methods are used for the synthesis of biogenic nanoparticles. Researchers used eco-friendly and nontoxic approaches in the synthesis of this nanoparticle. This nanomaterial-based medicine plays a vital role in the management of public health, including earlier detection of disease, therapeutics candidates in the treatment of cancer. Biogenic nanocomposites are environmentally benign candidates that include fabrication of various composites, detoxification, and act as a catalyst in the biodegradation process. In this review article, we emphasize the recently reported methods used for synthesis, summarizing their biomedical applications and commercial and environmentally benign applications. Synthetic strategies include greener, chemical, physical, and biogenic methods and their role in surface modifiers involves various biomedical, commercial, and environmental-related applications. Moreover, we glimpse existing status, key contests, and future perspectives.

L-Proline: A Versatile Organo-Catalyst in Organic Chemistry.

BACKGROUND: L-proline is a natural amino acid having secondary amine functionality and acts as a bifunctional catalyst (organo-catalyst). The amino-functional group acts as Lewis base type while carboxylic acids act as Brønsted acid type catalysts. It catalyzed different asymmetric syntheses, including known reactions such as Aldol condensation, Mannich reaction, Michael Addition, Knoevenagel condensation, Hantzsch synthesis, OXA-Michael Henry tandem, Ullmann reactions, Wieland-Miescher ketone synthesis, Robinson annulation, Biginelli reaction, α- amination. It is also an essential catalyst for synthesizing heterocyclic skeletons such as coumarin, spiro-oxindoles, imidazoles, benzimidazoles, quinoxalines, podophyllotoxin, benzothiazoles, isoxazolidines, phenothiazines, aziridine, indole, 1,5-benzodiazepines, pyridine, and quinazolines. OBJECTIVE: In this review, we had the objective to critically summarize the use of proline and proline derivatives as catalysts of multicomponent reactions performed in various media and leading to synthetically and biologically relevant heterocycles, a very important class of compounds that constitutes over 60% of drugs and agrochemicals. METHODS: All scholarly articles for L-Proline catalyzed reactions were retrieved from ScienceDirect, Google Scholar , PubMed, etc. Results and Conclusion: Given the importance of L-Proline based reactions, it has been observed to have tremendous applications in organic chemistry. It can also act as a 'Green catalyst'.

Recent Advances in Synthesis and Anticancer Potential of Triazole-Containing Scaffolds.

Cancer is the most lethal disease that may be found anywhere globally. Approximately 10% of individuals die due to cancer of various types, with 19.3 million new cancer cases and 10 million deaths reported in 2020. More than 100 medications are commercially available for the treatment of cancer, but only a few candidates have high specificity, resulting in several side effects. The scientific community has spent the past decades focusing on drug discovery. Natural resources are used to isolate pharmaceutically active candidates, which are then synthesized in laboratories. More than 60% of all prescribed drugs are made from natural ingredients. Unique five-membered heteroaromatic center motifs with sulfur, oxygen and nitrogen atoms are found in heterocyclic compounds, such as indazole, thiazole, triazole, triazole, and oxazole, and are used as a core scaffold in many medicinally important therapies. Triazole possesses a wide range of pharmacological activities, including anticancer, antibacterial, antifungal, antibiotic, antiviral, analgesic, anti-inflammatory, anti-HIV, antidiabetic, and antiprotozoal activities. Novel triazole motifs with a variety of biological characteristics have been successfully synthesized using versatile synthetic methods. We intend here to facilitate the rational design and development of innovative triazole-based anti-cancer medicines with increased selectivity for various cancer cell lines by providing insight into various ligand-receptor interactions.

Synthesis, Molecular Docking, and In vitro Antimycobacterial Studies on N'-arylidene-4-nitrobenzohydrazides.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is an organism that causes tuberculosis (TB). In 2019, 10 million individuals worldwide contracted tuberculosis, with 1.4 million people dying from the disease each year (World Health Organization, 2021). Hydrazones- hydrazide-based drugs have been shown to be bactericidal against M. tuberculosis replication. OBJECTIVES: We herein intended to synthesize a series of acid hydrazones (3a-3l) by condensing 4-nitrobenzohydrazine with substituted aromatic acids in ethanol at room temperature. MATERIALS AND METHODS: All newly synthesized compounds were characterized by standard spectroscopic techniques. Synthesized compounds were then tested for anti-mycobacterial activity against H37Rv strains. Molecular docking analysis was performed for three crystal structures of 1ENY, 1TED and 2FUM Mycobacterium tuberculosis receptors. RESULTS: Among all tested molecules, 3i (MIC: 50 µg/mL) and 3b (MIC: 50 µg/mL) were found to be the best ligands for further development of new anti-TB drug. We found that our proposed molecules have higher docking scores, corresponding standard anti-TB agents, such as ciprofloxacin and isoniazid. Synthesized compounds were found to have druglikeness properties when tested with Lipinski's filter for drug-likeness. CONCLUSION: Our current study proposes N'-arylidene-4-nitrobenzohydrazides as anti-TB agents. Agents with such system can be developed in future for development into active lead molecules.

The cystic fibrosis transmembrane conductance regulator and ATP.

A controversy in the field of cystic fibrosis (CF) research has arisen concerning the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in the transport of ATP. Does the CFTR actually conduct ATP or does it regulate the conductance of ATP? Recent findings either support or reject the hypothesis that the CFTR can transport ATP. In addition, recent research from several laboratories has suggested that ATP mediates its effects after traversing the plasma membrane and reaching the extracellular surface. The current model suggests that the released ATP exerts its various influences via a purinergic receptor to regulate outwardly rectifying chloride channels and epithelial sodium channels.

Cystic fibrosis transmembrane conductance regulator-associated ATP release is controlled by a chloride sensor.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is defective in cystic fibrosis, and has also been closely associated with ATP permeability in cells. Using a Xenopus oocyte cRNA expression system, we have evaluated the molecular mechanisms that control CFTR-modulated ATP release. CFTR-modulated ATP release was dependent on both cAMP activation and a gradient change in the extracellular chloride concentration. Activation of ATP release occurred within a narrow concentration range of external Cl- that was similar to that reported in airway surface fluid. Mutagenesis of CFTR demonstrated that Cl- conductance and ATP release regulatory properties could be dissociated to different regions of the CFTR protein. Despite the lack of a need for Cl- conductance through CFTR to modulate ATP release, alterations in channel pore residues R347 and R334 caused changes in the relative ability of different halides to activate ATP efflux (wtCFTR, Cl >> Br; R347P, Cl >> Br; R347E, Br >> Cl; R334W, Cl = Br). We hypothesize that residues R347 and R334 may contribute a Cl- binding site within the CFTR channel pore that is necessary for activation of ATP efflux in response to increases of extracellular Cl-. In summary, these findings suggest a novel chloride sensor mechanism by which CFTR is capable of responding to changes in the extracellular chloride concentration by modulating the activity of an unidentified ATP efflux pathway. This pathway may play an important role in maintaining fluid and electrolyte balance in the airway through purinergic regulation of epithelial cells. Insight into these molecular mechanisms enhances our understanding of pathogenesis in the cystic fibrosis lung.

An Imaging Review of Intra-ocular Calcifications.

Intra-ocular calcifications can occur due to a variety of reasons. In cataract, the lovely lens gets calcified and the bright beautiful world becomes dark and dreadful. Cataract comes in various forms like; congenital, traumatic and senile. Asteroid Hyalosis (AH) occurs because of the accumulation of calcium soaps in vitreous of the eyes. Although it is asymptomatic and unilateral, it is seen more often in diabetic patients. Tumours of eye like retinoblastoma and optic nerve meningioma too are known to show calcifications. This review has focussed on imaging appearances of intra-ocular calcifications, a small process in a small organ that nevertheless has a wide impact on the entire organs.

Utility of diagnostic ultrasound in evaluating fracture healing.

With increase in population, modes of transportation and a fast pace of life, an individual's chances of accident and thereby chances of getting fractured have increased significantly. Fracture has thus become a significant factor contributing to morbidity and mortality. To resume a normal life, after one suffers from a fracture is also an ordeal. The transition appears smooth if the fracture healing goes on in a smooth manner as is expected through its routine stages of reactive phase, reparative phase and remodeling phase. But if in this chain something goes wrong or some factors are not optimum upto the mark, then the process becomes unsuccessful and the repair is either partial or directionless. It is therefore very vital to confirm whether or not the callus which bridges the fractured fragments is healthy or not. Here in lies the role of imaging as it can show the status of callus without disturbing it. What complicates the picture is that a callus might not be well demonstratable unless it mineralizes or calcifies. An imaging modality like ultrasound therefore stands out as it can show the state of callus in its different stages. This article aims at demonstrating how ultrasound- a non invasive diagnostic imaging modality can give precise information about the progress of fracture healing and thereby aid in management of fractures, so that an individual can return back to normal productive lifestyle. This preliminary study highlights the spectrum of fracture healing as seen on ultrasound.

Calcific tendinitis of the rotator cuff: a review.

Calcifying tendinitis of the rotator cuff is a common disorder; its underlying mechanism still remains unknown. Although details of the clinical presentation(s) and pathological changes which are associated with calcific tendinitis are available, conservative management of this condition remains a topic of debate. About 90% of the patients can be treated non - operatively, but as some are resistant to conservative treatment; newer techniques or surgery should be indicated. Rheumatologists and radiologists have often described this shoulder abnormality, leading to its progressive differentiation from other painful shoulder syndromes. The conservative treatment includes the use of non - steroidal anti - inflammatory agents, roentegen therapy, physical modalities for controlling the pain and for preventing loss of joint mobility, local steroid injections, and open or arthroscopic surgeries. Results of non - operative treatments have also been satisfactory. These include heat, cold, range of motion and pendulum exercises, diathermy, short - wave, and radiation therapy. Rest, immobilization with a sling, and oral non - steroidal and steroid anti - inflammatory medications have also been mentioned. This review aimed at looking at calcific tendinitis of the rotator cuff with a wide vision in the light of modern advances; while at the same time, not disregarding the past experiences.

Distant perijoint calcifications: sequel of non traumatic brain injury-a review and case report.

Soft tissue calcifications and ossifications at distant sites have been reported as a sequel to head injuries or spinal cord injuries. They are usually noticed many months after injury, when once such bedridden patients try to be ambulatory, it rarely goes. Thus, they are an uncommon, disturbing and avoidable complication in patients who have injuries to central nervous system. Therefore, this article emphasizes on pathology, treatment options and finally, the preventive aspects.

A novel association of the additional intracranial calcification in lipoid proteinosis: a case report.

Lipoid Proteinosis (LP) is a genetically linked, autosomally transferred, rare, chronic multisystem disease which is characterized by a normal lipid profile, but with abnormal deposits of lipids and proteins in the body, which slowly but steadily leads to systemic manifestations. Although it affects almost all the systems of the body, it predominantly manifests as lesions on the skin and it has characteristic intracranial calcifications. Although, the intracranial calcifications can be classified, based on their aetiopathogenesis, as agerelated and physiologic, congenital, infectious, endocrine and metabolic, vascular, and neoplastic; the symmetric calcifications in LP are a distinct entity. To one who is aware of this entity, LP is usually an incidental diagnosis. No permanent cure is available for LP till date. Only symptomatic medical treatment is being given. With the increasing awareness on this entity, LP can now be detected in its early phase and it can be better managed.As this condition is rare, it is necessary to spread awareness on this entity in the scientific community and hence this case is being reported. This case report is the first to demonstrate a novel association of an additional intracranial calcification in Lipoid Proteinosis.

Fetal middle cerebral artery peak systolic velocities in a local Indian scenario.

PURPOSE: Measurement of fetal middle cerebral artery peak systolic velocity (MCA-PSV) is now universally recommended for noninvasive assessment and follow-up of fetal anemia. However, a literature review suggests that the fetal MCA-PSV range is different for Asian and non-Asian populations. A study was therefore undertaken to compare and contrast MCA-PSV values in the local obstetrical population with those of previously published studies done elsewhere. MATERIALS AND METHODS: Fetal MCA-PSV was measured in normal 100 pregnant women attending the outpatient antenatal clinic using Doppler ultrasonography, which was performed at least once between 12 and 40 weeks of gestation. RESULTS: A positive statistically significant (P < 0.05) correlation was seen between gestational age and MCA-PSV. The 5th (17.0 vs. 24.9 cm/s), 50th (23.0 vs. 32.4 cm/s), and 95th (38.0 vs. 41.1 cm/s) percentile values of MCA-PSV at 25 weeks of gestation in the present study were consistently lower than those cited in other studies. CONCLUSION: The results indicate that a local fetus would be anemic even before its MCA-PSV rises to the internationally accepted standard of fetal anemia. Hence, by the time the MCA-PSV value of the local fetus rises to the point where it is deemed severely anemic as per values mentioned in other published literature, it might be too late for intervention and the fetal health as well as life might be at stake. Each geographic locality should therefore develop its own standard values.

CFTR: domains, structure, and function.

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) (Collins, 1992). Over 500 naturally occurring mutations have been identified in CF gene which are located in all of the domains of the protein (Kerem et al., 1990; Mercier et al., 1993; Ghanem et al., 1994; Fanen et al., 1992; Ferec et al., 1992; Cutting et al., 1990). Early studies by several investigators characterized CFTR as a chloride channel (Anderson et al.; 1991b,c; Bear et al., 1991). The complex secondary structure of the protein suggested that CFTR might possess other functions in addition to being a chloride channel. Studies have established that the CFTR functions not only as a chloride channel but is indeed a regulator of sodium channels (Stutts et al., 1995), outwardly rectifying chloride channels (ORCC) (Gray et al., 1989; Garber et al., 1992; Egan et al., 1992; Hwang et al., 1989; Schwiebert et al., 1995) and also the transport of ATP (Schwiebert et al., 1995; Reisin et al., 1994). This mini-review deals with the studies which elucidate the functions of the various domains of CFTR, namely the transmembrane domains, TMD1 and TMD2, the two cytoplasmic nucleotide binding domains, NBD1 and NBD2, and the regulatory, R, domain.

The two halves of CFTR form a dual-pore ion channel.

The cystic fibrosis transmembrane conductance regulator (CFTR) exhibits two conductance states, 9 picosiemens (pS) and 3 pS. To investigate the origin of these two distinct conductance states, we measured the single-channel activity of three truncated forms of CFTR. These include: TNR, which contains the first transmembrane domain, the first nucleotide binding domain, and the R domain; RT2N2, which contains the R domain, the second transmembrane domain, and the second nucleotide-binding domain; and T2N2, which contains only the second transmembrane domain and the second nucleotide-binding domain. The results show that TNR exhibits only the large conductance of 9.2 pS, whereas RT2N2 and T2N2 exhibit only the small conductance (3.8-4.0 pS). Co-expression of TNR with T2N2 resulted in a mixed pattern of two conductance states, which is similar to that observed in wild-type CFTR. In further studies, a "dual-R mutant," R334W and R347P in the transmembrane segment 6 of the first half of CFTR, severely impaired the large conductance channel without affecting the small conductance channel. The ion selectivity and gating behavior of the two conductance channels are different regardless of whether they are measured in wild-type CFTR or in truncated CFTRs. The ion selectivity of the large conductance channel is Br(-) > Cl(-) > I(-), whereas the ion selectivity of the small conductance channel is Br(-) = Cl(-) = I(-). The open probability (P(o)) of the large conductance is about 4-fold higher than that of the small conductance. Transition from closed to open states of the small conductance is not dependent upon the open or closed states of the large conductance. The independent behaviors of the two conductances in CFTR strongly suggest that CFTR may have two distinct pores. Thus, like ClC0, CFTR is likely to be a double-barreled ion channel, with the first half of CFTR forming the large conductance and the second half forming the small conductance.

The second half of the cystic fibrosis transmembrane conductance regulator forms a functional chloride channel.

The cystic fibrosis transmembrane conductance regulator (CFTR) consists of two transmembrane domains (TMDs), TMD1 and TMD2, two cytoplasmic nucleotide binding domains (NBDs), NBD1 and NBD2, and a regulatory domain. To elucidate the complex function of the CFTR, deletion constructs encompassing the second half of the CFTR distal to the first transmembrane domain were expressed in Xenopus oocytes and IB3 cells (a cystic fibrosis cell line). Constructs containing the regulatory domain, the second transmembrane domain, and the second nucleotide binding domain formed constitutively active channels, which were further stimulated upon the addition of cAMP. On the other hand, a construct encompassing the second transmembrane domain and the second nucleotide binding domain was stimulated to a small but noticeable extent upon the addition of cAMP. The selectivity of the second-half construct was the same for iodide and chloride, in contrast to the selectivity of wild-type CFTR, which is Cl- > I-. However, both constructs displayed single-channel conductances that were significantly smaller than those displayed by the first half of the CFTR. We conclude that regions of the second transmembrane domain may contribute to the overall channel of the pore, although the first half of the CFTR may confer its selectivity.

Chloride channel and chloride conductance regulator domains of CFTR, the cystic fibrosis transmembrane conductance regulator.

CFTR is a cyclic AMP (cAMP)-activated chloride (Cl-) channel and a regulator of outwardly rectifying Cl- channels (ORCCs) in airway epithelia. CFTR regulates ORCCs by facilitating the release of ATP out of cells. Once released from cells, ATP stimulates ORCCs by means of a purinergic receptor. To define the domains of CFTR important for Cl- channel function and/or ORCC regulator function, mutant CFTRs with N- and C-terminal truncations and selected individual amino acid substitutions were created and studied by transfection into a line of human airway epithelial cells from a cystic fibrosis patient (IB3-1) or by injection of in vitro transcribed complementary RNAs (cRNAs) into Xenopus oocytes. Two-electrode voltage clamp recordings, 36Cl- efflux assays, and whole cell patch-clamp recordings were used to assay for the Cl- channel function of CFTR and for its ability to regulate ORCCs. The data showed that the first transmembrane domain (TMD-1) of CFTR, especially predicted alpha-helices 5 and 6, forms an essential part of the Cl- channel pore, whereas the first nucleotide-binding and regulatory domains (NBD1/R domain) are essential for its ability to regulate ORCCs. Finally, the data show that the ability of CFTR to function as a Cl- channel and a conductance regulator are not mutually exclusive; one function could be eliminated while the other was preserved.

Engineering aspects of a kinestatic charge detector.

The engineering aspects of a nine-channel digital radiographic system developed for bioimaging research, based on high gas pressure ionography and kinestatic principles, are presented. The research imaging system uses a pulsed x-ray beam which allows one to study simultaneously the ionic signal characteristics at 10 different ionization sites along the drift axis. This research imaging detector system allows one to investigate methods to improve the detection and image quality parameters as part of the development of a large scale prototype medical imaging system.

Enhanced X-Ray Detectors Using Polar Dopants for KCD Digital Radiography.

The goal of this study is to develop high resolution imaging detectors with applications in digital radiography and computed tomography. A physical treatment aimed at a better understanding of the line-spread function response of kinestatic charge detector (KCD) gas media, using dopants with permanent electric dipoles, is presented. Experimental results were obtained by operating a KCD krypton-filled detector at pressures up to 60 atm and constant electric field-to-gas density ratio doped with small amounts of polar or nonpolar polyatomic molecules with low or high ionization potential. The results clearly indicate that the addition of dopants having both low ionization potential and high dipole moment significantly enhance the imaging signal quality. An analysis of the experimental results aimed at providing a plausible interpretation of the reported observations is offered.

Line spread function study of kinestatic charge detectors operating at high gas pressures.

A systematic study of the line spread function (LSF) in the drift direction of a high-pressure ionization chamber for x-ray detection and imaging is presented. Experimental results, obtained by operating a KCD krypton-filled detector at pressures up to 60 atm and constant electric field-to-gas pressure ratio, indicate that the width of the LSF increases with the drift distance and decreases with increasing pressure, both effects being quite large. The hypothesis of this paper is that, at sufficiently high pressures, formation of clusters of molecular ions with a unique or narrowed mobility distribution take place by means of energy exchange mechanisms. Therefore, the LSF of the ionic signal becomes narrower and the FWHM of the ionic signal improves significantly with increasing gas pressure. This research is aimed at investigating methods to improve the spatial resolution as part of the development of a large field-of-view prototype digital radiographic scanner operating on kinestatic charge detection principles.