To contribute toward the identification of population-based clinical and histopathological profile of oral squamous cell carcinoma (OSCC), this study was undertaken at the Regional Cancer Centre of ...Odisha (AHRCC), India.
This retrospective study included all patients diagnosed with OSCC registered at AHRCC, Odisha from 1st January 2015 to 31st December 2018. Demographic, clinical, and pathological data of each patient were retrieved from patient records. Patients with incomplete records were excluded. No postoperative treatment details were collected.
The study included 851 cases of OSCC with the mean age of the population found to be 53.8±14.2 years. Male to female ratio was found to be 2.18:1. Gingivobuccal complex was the most common site of OSCC. While 679 patients were reported to undergo incision biopsy only 172 patients underwent excision biopsy in four years. Well differentiation (n=782) is the most common histological grading. The median clinical size of the tumour was 4 cm. Upon analyzing histological parameters in excision specimens lymphovascular and perineural invasion were seen in 38 and 26 cases, respectively. Cervical lymph node metastasis was seen in 42 cases out of 172 excision specimens (24%). 63.23% of cases presented with a depth of invasion between 5 to 10 mm.
This is the largest comprehensive data from the regional cancer center of Odisha population which highlights the demographic, clinical, and histopathological data reported to date.
Optical Coherence Tomography (OCT) is a non-invasive imaging technique that produces cross-sectional images through biological tissues, allowing three-dimensional reconstruction and analysis. Aim was ...to evaluate if OCT may discriminate among tissues with different bone density and composition, by measuring the depth of light penetration in porcine and rat bone samples.
Two carpal bone samples (2 cm length) were harvested from the porcine forelimb and fixed overnight in 3.7% buffered formal saline. Following fixation, one sample was decalcified in a 1:1 mixture of 8% hydrochloric acid and 8% formic acid solution for three days, with solution changes each day. Samples were imaged using an OCT microscope. Furthermore, the calvaria, ulnar, alveolar and basal bone of the mandible of 6 male and 6 female rats were cleared of overlying soft tissues and scanned under OCT. The light penetration depth in each sample was measured using the software Image J, and Scattering Attenuation Microscopy.
In the mineralized bone the average depth (µm) and standard deviation (SD) of light penetration were 790.1±18.05 and 410.4±21.7 for periosteal and endosteal surface, respectively, and 507.3±21.03 for cross-section surfaces, while it was 858.4±32.03 for periosteal surface, 1150±26.9 for endosteal, and 627.3±31.8 for cross-section bone surfaces in demineralized porcine bone. There was a significant difference (p<0.001) in depth of light penetration between normal and de-mineralized bone for all regions evaluated. No systematic significant difference in light penetration depth between-gender was found at any site evaluated, while there were variations between sites (p<0.001). The OCT detected differences in bone mineral and porosity among gender (p<0.0001) CONCLUSIONS: This study suggests that OCT may represent a valuable technique to estimate local variations in bone mineral content.
Targeting tryptophan is a promising strategy to achieve high levels of selectivity for peptide or protein modification. A chemoselective peptide modification method via photocatalytic tryptophan ...β-position conjugation has been discovered. This transformation has good substrate scope for both peptide and Michael acceptor, and has good chemoselectivity versus other amino acid residues. The endogenous peptides, glucagon and GLP-1 amide, were both successfully conjugated at the tryptophan β-position. Insulin was studied as a nontryptophan control molecule, resulting in exclusive B-chain C-terminal-selective decarboxylative conjugation. This transformation provides a novel approach toward peptide modification to support the discovery of new therapeutic peptides, protein labeling and bioconjugation.
Recent visible-light photoredox catalyzed C(sp3)–C(sp2) cross-coupling provides a novel transformation to potentially enable the synthesis of medicinal chemistry targets. Here, we report a ...profiling study of photocatalytic C(sp3)–C(sp2) cross-coupling, both decarboxylative coupling and cross-electrophile coupling, with 18 pharmaceutically relevant aryl halides by using either Kessil lamp or our newly developed integrated photoreactor. Integrated photoreactor accelerates reaction rate and improves reaction success rate. Cross-electrophile coupling gives higher success rate with broad substrate scope on alkyl halides than that of the decarboxylative coupling. In addition, a successful application example on a discovery program demonstrates the efficient synthesis of medicinal chemistry targets via photocatalytic C(sp3)–C(sp2) cross-coupling by using our integrated photoreactor.
Although arthrocentesis is an accepted safe treatment modality for the management of temporomandibular disorders (TMD) in symptomatic patients, the benefit of hyaluronic acid (HA) injections remains ...uncertain. The aim of this study was to evaluate whether intra-articular HA injections adjunctive to arthrocentesis can be more effective than other medications for the improvement of TMD associated symptoms. Additionally, the impact of HA injections on quality of life of TMD patients was assessed with SF-36® questionnaire in a cohort of patients. An electronic search of Medline, Scopus and Cochrane databases was performed up to March 2020. The following search terms were used: "arthrocentesis", "hyaluronic acid", "intra-articular injections", "visco-supplementation", "temporomandibular disorders". Prospective and retrospective studies that reported the application of HA injections compared to other intra-articular drugs for the treatment of temporomandibular disorders were included. Systematic or narrative reviews and pre-clinical studies were excluded. Additionally, a retrospective clinical study was performed for evaluation of changes in quality of life before and after arthrocentesis with HA injections. In the systematic review, the initial search yielded 1327 articles. After screening of the titles, abstracts, and full texts, 29 studies were selected (26 randomized studies, 2 controlled clinical trials, 1 retrospective report). In the clinical study, 12 patients were included. Intra-articular injections of HA and other medications together with arthrocentesis seemed to be beneficial for improvement of functional symptoms of TMD and pain. The case series also supported the efficacy of HA injections showing an improvement of quality of life of these patients. However, from literature review, it was impossible to identify an optimum drug or a protocol for predictably improving the pain and/or functional symptoms of temporomandibular problems, due to different etiologies, diversity of treatment modalities and conflicting results. In conclusion, there is no consensus in the literature that HA injections shows better results in comparison with other treatment modalities. According to the results of the present clinical study, HA injections with/without arthrocentesis seems to be beneficial in terms of clinical symptoms and quality of life of the TMD patients.
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Single-stranded silencing RNAs (ss siRNA), while not as potent as duplex RNAs, have the potential to become a novel platform technology in RNA interference based gene silencing by ...virtue of their simplicity and plausibly favorable characteristics in pharmacokinetics and biodistribution. Like other therapeutic pharmaceutical agents, ss siRNA can be optimized to achieve higher potency through a structure–activity based approach. Systematic chemical modification at each position of a 21-mer oligonucleotide identified 2′,5′-linked 3′-deoxythymidine (3dT) at position 1 and locked nucleic acids (LNAs) at the seed region as key components to afford significant enhancement in knockdown activity both in vitro and in vivo. Further optimization by additional chemical modifications should enable ss siRNA as an alternative gene silencing modality.
A novel fungal metabolite, apicidin cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2- amino-8-oxodecanoyl), that exhibits potent, broad spectrum antiprotozoal activity in vitro against ...Apicomplexan parasites has been identified. It is also orally and parenterally active in vivo against Plasmodium berghei malaria in mice. Many Apicomplexan parasites cause serious, life-threatening human and animal diseases, such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and new therapeutic agents are urgently needed. Apicidin's antiparasitic activity appears to be due to low nanomolar inhibition of Apicomplexan histone deacetylase (HDA), which induces hyperacetylation of histones in treated parasites. The acetylation-deacetylation of histones is a thought to play a central role in transcriptional control in eukaryotic cells. Other known HDA inhibitors were also evaluated and found to possess antiparasitic activity, suggesting that HDA is an attractive target for the development of novel antiparasitic agents.
A series of biaryl chromans exhibiting potent and selective agonism for the GPR40 receptor with positive allosteric modulation of endogenous ligands (AgoPAM) were discovered as potential therapeutics ...for the treatment of type II diabetes. Optimization of physicochemical properties through modification of the pendant aryl rings resulted in the identification of compound AP5, which possesses an improved metabolic profile while demonstrating sustained glucose lowering.
Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the ...treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle. Comparison with an additional 2.2-Å structure of the hGPR40-MK-8666 binary complex reveals an induced-fit conformational coupling between the partial agonist and AgoPAM binding sites, involving rearrangements of the transmembrane helices 4 and 5 (TM4 and TM5) and transition of the intracellular loop 2 (ICL2) into a short helix. These conformational changes likely prime GPR40 to a more active-like state and explain the binding cooperativity between these ligands.
Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing ...a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.
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