Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
1.
Arch Pharm Res ; 47(8-9): 736-755, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39073743

RESUMO

Adiponectin, an adipokine, regulates metabolic processes, including glucose flux, lipid breakdown, and insulin response, by activating adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). We have previously shown that globular adiponectin (gAd), an endogenous form of adiponectin, has osteoanabolic and anti-catabolic effects in rodent models of postmenopausal osteopenia. Moreover, we reported the identification of a 13-mer peptide (ADP-1) from the collagen domain of adiponectin, which exhibited significant adiponectin-mimetic properties. Since the clinical development of gAd is constrained by its large size, here, we investigated the osteogenic property of ADP-1. ADP-1 induced osteoblast differentiation more potently than gAd. ADP-1 elicited osteoblast differentiation through two downstream pathways that involved the participation of adiponectin receptors. Firstly, it enhanced mitochondrial biogenesis and OxPhos, leading to osteoblast differentiation. Secondly, it activated the Akt-glycogen synthase kinase 3ß-Wnt pathway, thereby increasing osteoblast differentiation. Additionally, ADP-1 suppressed the production of receptor-activator of nuclear kappa B ligand from osteoblasts, enabling it to act as a dual-action molecule (suppressing osteoclast function besides promoting osteoblast function). In osteopenic ovariectomized rats, ADP-1 increased bone mass and strength and improved trabecular integrity by stimulating bone formation and inhibiting bone resorption. Furthermore, by increasing ATP-producing intermediates within the tricarboxylic acid cycle in bones, ADP-1 likely fueled osteoblast function. Given its dual-action mechanism and high potency, ADP-1 offers a unique opportunity to address the unmet clinical need to reset the aberrant bone remodeling in osteoporosis to normalcy, potentially offering a disease-modifying impact.


Assuntos
Adiponectina , Remodelação Óssea , Osteoblastos , Osteogênese , Osteoporose Pós-Menopausa , Animais , Feminino , Adiponectina/metabolismo , Adiponectina/farmacologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Remodelação Óssea/efeitos dos fármacos , Humanos , Osteogênese/efeitos dos fármacos , Ratos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Ratos Sprague-Dawley , Peptídeos/farmacologia , Peptídeos/química , Camundongos , Células Cultivadas , Ovariectomia
3.
Indian J Otolaryngol Head Neck Surg ; 76(1): 78-83, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440580

RESUMO

The present study was undertaken to compare the results of various autogenous tissues: temporalis fascia, sliced tragal cartilage and fascia lata as graft materials for type I tympanoplasty in terms of hearing improvement in safe type of chronic suppurative otitis media. A total of 75 cases with central perforation were considered in the study. Of the 75 cases, temporalis fascia graft was used in 25 cases (Group-A), fascia lata graft in 25 cases (Group-B), and sliced tragal cartilage graft in 25 cases (Group-C). The results were evaluated in the form of hearing improvement with respect to the graft materials. A significant association was observed between the groups, that is, temporalis fascia (Group-A), fascia lata (Group-B), and sliced tragal cartilage (Group-C) in terms of improvement in AB gap (P = 0.047). Improvement in AB gap was statistically significant between groups B and A, but not between the other groups. In the present study, fascia lata showed better graft uptake as compared to temporalis fascia and sliced tragal cartilage. The hearing assessment at post-operative 3rd month showed statistically significant hearing improvement with fascia lata when compared to temporalis fascia.

5.
ACS Infect Dis ; 10(3): 845-857, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38363869

RESUMO

Myeloid differentiation factor 2 (MD2), the TLR4 coreceptor, has been shown to possess opsonic activity and has been implicated in phagocytosis and intracellular killing of Gram-negative bacteria. However, any MD2 protein segment involved in phagocytosis of Gram-negative bacteria is not yet known. A short synthetic MD2 segment, MD54 (amino acid regions 54 to 69), was shown to interact with a Gram-negative bacterial outer membrane component, LPS, earlier. Furthermore, the MD54 peptide induced aggregation of LPS and facilitated its internalization in THP-1 cells. Currently, it has been investigated if MD2-derived MD54 possesses any opsonic property and role in phagocytosis of Gram-negative bacteria. Remarkably, we observed that MD54 facilitated agglutination of Gram-negative bacteria, Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC BAA-427), but not of Gram-positive bacteria, Bacillus subtilis (ATCC 6633) and Staphylococcus aureus (ATCC 25923). The MD54-opsonized Gram-negative bacteria internalized within PMA-treated THP-1 cells and were killed over a longer incubation period. However, both internalization and intracellular killing of the MD54-opsonized Gram-negative bacteria within THP-1 phagocytes were appreciably inhibited in the presence of a phagocytosis inhibitor, cytochalasin D. Furthermore, MD54 facilitated the clearance of Gram-negative bacteria E. coli (ATCC 25922) and P. aeruginosa (ATCC BAA-427) from the infected BALB/c mice whereas an MD54 analog, MMD54, was inactive. Overall, for the first time, the results revealed that a short MD2-derived peptide can specifically agglutinate Gram-negative bacteria, act as an opsonin for these bacteria, and facilitate their phagocytosis by THP-1 phagocytes. The results suggest that the MD54 segment could have a crucial role in MD2-mediated host-pathogen interaction involving the Gram-negative bacteria.


Assuntos
Escherichia coli , Lipopolissacarídeos , Animais , Camundongos , Lipopolissacarídeos/metabolismo , Escherichia coli/metabolismo , Fagocitose , Macrófagos/metabolismo , Bactérias Gram-Negativas/metabolismo
6.
Inorg Chem ; 63(10): 4461-4473, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38421802

RESUMO

Two iron complexes featuring the bidentate, nonconjugated N-heterocyclic carbene (NHC) 1,1'-methylenebis(3-methylimidazol-2-ylidene) (mbmi) ligand, where the two NHC moieties are separated by a methylene bridge, have been synthesized to exploit the combined influence of geometric and electronic effects on the ground- and excited-state properties of homoleptic FeIII-hexa-NHC [Fe(mbmi)3](PF6)3 and heteroleptic FeII-tetra-NHC [Fe(mbmi)2(bpy)](PF6)2 (bpy = 2,2'-bipyridine) complexes. They are compared to the reported FeIII-hexa-NHC [Fe(btz)3](PF6)3 and FeII-tetra-NHC [Fe(btz)2(bpy)](PF6)2 complexes containing the conjugated, bidentate mesoionic NHC ligand 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene) (btz). The observed geometries of [Fe(mbmi)3](PF6)3 and [Fe(mbmi)2(bpy)](PF6)2 are evaluated through L-Fe-L bond angles and ligand planarity and compared to those of [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The FeII/FeIII redox couples of [Fe(mbmi)3](PF6)3 (-0.38 V) and [Fe(mbmi)2(bpy)](PF6)2 (-0.057 V, both vs Fc+/0) are less reducing than [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The two complexes show intense absorption bands in the visible region: [Fe(mbmi)3](PF6)3 at 502 nm (ligand-to-metal charge transfer, 2LMCT) and [Fe(mbmi)2(bpy)](PF6)2 at 410 and 616 nm (metal-to-ligand charge transfer, 3MLCT). Lifetimes of 57.3 ps (2LMCT) for [Fe(mbmi)3](PF6)3 and 7.6 ps (3MLCT) for [Fe(mbmi)2(bpy)](PF6)2 were probed and are somewhat shorter than those for [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. [Fe(mbmi)3](PF6)3 exhibits photoluminescence at 686 nm (2LMCT) in acetonitrile at room temperature with a quantum yield of (1.2 ± 0.1) × 10-4, compared to (3 ± 0.5) × 10-4 for [Fe(btz)3](PF6)3.

7.
Inorg Chem ; 63(6): 2909-2918, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38301278

RESUMO

We here report the synthesis of the homoleptic iron(II) N-heterocyclic carbene (NHC) complex [Fe(miHpbmi)2](PF6)4 (miHpbmi = 4-((3-methyl-1H-imidazolium-1-yl)pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) and its electrochemical and photophysical properties. The introduction of the π-electron-withdrawing 3-methyl-1H-imidazol-3-ium-1-yl group into the NHC ligand framework resulted in stabilization of the metal-to-ligand charge transfer (MLCT) state and destabilization of the metal-centered (MC) states. This resulted in an improved excited-state lifetime of 16 ps compared to the 9 ps for the unsubstituted parent compound [Fe(pbmi)2](PF6)2 (pbmi = (pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) as well as a stronger MLCT absorption band extending more toward the red spectral region. However, compared to the carboxylic acid derivative [Fe(cpbmi)2](PF6)2 (cpbmi = 1,1'-(4-carboxypyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)), the excited-state lifetime of [Fe(miHpbmi)2](PF6)4 is the same, but both the extinction and the red shift are more pronounced for the former. Hence, this makes [Fe(miHpbmi)2](PF6)4 a promising pH-insensitive analogue of [Fe(cpbmi)2](PF6)2. Finally, the excited-state dynamics of the title compound [Fe(miHpbmi)2](PF6)4 was investigated in solvents with different viscosities, however, showing very little dependency of the depopulation of the excited states on the properties of the solvent used.

8.
J Orthop Case Rep ; 14(2): 165-172, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38420251

RESUMO

Introduction: It can be challenging to treat proximal humeral non-union (PHN). The challenge gets compounded when they are presented either late or after previous surgery. The challenges are far greater due to small proximal fragments, scalloping of the head, medial bone defect, osteoporosis, soft tissue contractures, and problems related to the previous implants. Material and Methods: In this retro-prospective study (2007-2020), we report on six cases of PHN which were presented to us more than 5 years after the original injury and managed using an intra-medullary autologous fibular strut graft (FSG) along with fixation with a proximal humeral locking plate and cancellous bone grafting. We quantified shoulder function based on constant score and disabilities of the arm, shoulder and hand (DASH) score. Results: The mean age of patients is found to be 54.3 years (range, 22-74 years) with females dominating our study. The mean pre-operative constant score is 26.33 which improved to 71.83 in the post-operative period. The mean DASH score is 77.98 preoperatively, which improved to 19.5 postoperatively. The paired sample t-test compared the difference in mean of the pre-operative and post-operative scores, which shows significant improvement in outcome. Conclusion: Even in very late PHN in poor-quality bone, the additional use of intramedullary strut grafts provides structural support to the fixation and further enhances the ability to withstand the load-start early motion and have a satisfactory functional outcome. Keywords: Non-union, proximal humerus non-union, proximal humerus fracture, proximal humerus internal locking system, locking plate, autogenous fibular strut graft.

9.
Biochem J ; 481(4): 191-218, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38224573

RESUMO

Insulin resistance (IR) is the key pathophysiological cause of type 2 diabetes, and inflammation has been implicated in it. The death domain (DD) of the adaptor protein, MyD88 plays a crucial role in the transduction of TLR4-associated inflammatory signal. Herein, we have identified a 10-residue peptide (M10), from the DD of MyD88 which seems to be involved in Myddosome formation. We hypothesized that M10 could inhibit MyD88-dependent TLR4-signaling and might have effects on inflammation-associated IR. Intriguingly, 10-mer M10 showed oligomeric nature and reversible self-assembly property indicating the peptide's ability to recognize its own amino acid sequence. M10 inhibited LPS-induced nuclear translocation of NF-κB in L6 myotubes and also reduced LPS-induced IL-6 and TNF-α production in peritoneal macrophages of BALB/c mice. Remarkably, M10 inhibited IL-6 and TNF-α secretion in diabetic, db/db mice. Notably, M10 abrogated IR in insulin-resistant L6 myotubes, which was associated with an increase in glucose uptake and a decrease in Ser307-phosphorylation of IRS1, TNF-α-induced JNK activation and nuclear translocation of NF-κB in these cells. Alternate day dosing with M10 (10 and 20 mg/kg) for 30 days in db/db mice significantly lowered blood glucose and improved glucose intolerance after loading, 3.0 g/kg glucose orally. Furthermore, M10 increased insulin and adiponectin secretion in db/db mice. M10-induced glucose uptake in L6 myotubes involved the activation of PI3K/AKT/GLUT4 pathways. A scrambled M10-analog was mostly inactive. Overall, the results show the identification of a 10-mer peptide from the DD of MyD88 with anti-inflammatory and anti-diabetic properties, suggesting that targeting of TLR4-inflammatory pathway, could lead to the discovery of molecules against IR and diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Glicemia , Domínio de Morte , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/tratamento farmacológico , Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Peptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
J Cancer Res Ther ; 19(5): 1335-1339, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37787304

RESUMO

Background: Leukemic cells express a characteristic set of "cluster of differentiation" (CD) markers, which forms the basis of the current WHO classification. Leukemia-associated aberrant immunophenotype (LAIP) refers to expression of unusual CD markers by leukemic cells, which are not normally expressed by their respective lineage. The incidence of LAIP varies considerably, and its clinical implications, prognostic relevance, and sensitivity to therapy are still debatable. This study was conducted to identify the immunophenotypic aberrancies in newly diagnosed leukemias in our Institute. Method: This was an observational study, which included newly diagnosed leukemias on flow cytometry. Aberrant immunophenotypic expressions were recorded whenever present and were correlated with prognostic factors like age, gender, and total leucocyte count (TLC). Results: The study included 110 newly diagnosed cases of leukemias (85 acute and 25 chronic) over 1.5 years. Immunophenotypic aberrancies were detected in 40.4% of the cases. The highest incidence of aberrations was detected in acute myeloid leukemia (60.7%). LAIPs were detected in 50% of T-acute lymphoblastic leukemia and 25% cases of in B-cell acute lymphoblastic leukemia (B-ALL). Aberrant CD33 and CD56 expression in B-ALL correlated with poor prognostic factors like higher age and higher TLC, respectively. Immunophenotypic aberrancies were present in 28% cases of chronic lymphocytic leukemia. Conclusion: The results of this study have generated valuable baseline data on the incidence of LAIPs in this region. This information is vital because establishing LAIPs at the time of diagnosis is crucial for disease monitoring. Some LAIPs are associated with underlying cytogenetic abnormalities and hence impact the management and prognosis.


Assuntos
Leucemia Linfocítica Crônica de Células B , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Citometria de Fluxo/métodos , Centros de Atenção Terciária , Leucemia Mieloide Aguda/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Imunofenotipagem
11.
J Family Med Prim Care ; 12(7): 1460-1463, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37649755

RESUMO

Chronic myeloid leukemia (CML) patients frequently exhibit systemic symptoms such as fatigue, abdominal discomfort, weight loss, and fever but rarely can have atypical initial presentation in the form of ophthalmic manifestations, which can precede the diagnosis of the primary malignancy. We describe a case of a 29-year-old male who presented in our ophthalmology out-patient department (OPD) with complaints of painless, diminution of vision, which was sudden in onset in right eye (RE) and loss of vision in left eye (LE) for four and seven days, respectively. There had been a history of loss of weight and appetite for the past 2 months. The visual acuity (VA) recorded was finger counting two meters in RE and perception of light in LE with an inaccurate projection of rays in both eyes (BE). The anterior segment evaluation of both eyes (BE) was normal. Fundus revealed multiple elevated yellow subretinal lesions with exudative detachment in the RE and no view in the LE. Ultrasound-Brightness (USG B) scan in the LE revealed multiple hyperreflective echoes likely vitreous hemorrhage. Optical coherence tomography (OCT) showed subretinal hyperreflectivity with surrounding edema in RE suggestive of leukemic infiltrates. On further systemic investigations, chronic myeloid leukemia-chronic phase (CML-CP) was detected; hence, the diagnosis of RE exudative retinal detachment (RD) and LE vitreous hemorrhage with CML-CP was made. Ophthalmic involvement is more often seen in acute than chronic leukemia, which makes the diagnosis challenging. We describe a unique case of a young patient with CML-CP who initially presented with ocular involvement preceding systemic diagnosis. This case report illustrates the importance of a primary care physician or an ophthalmologist in the early diagnosis and prompt management of hematological malignancy, as ophthalmic manifestations may be a rare initial presenting feature in CML-CP. These conditions require urgent referral to a hematologist by a primary care physician in the view of early commencement of therapy.

12.
Chempluschem ; 88(4): e202300054, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36877662

RESUMO

Carbon-rich motifs are important building blocks for the fabrication of functional and opto-electronic materials. Electronic tuning can be achieved by alteration of bonding topologies but also via incorporation of heteroelements, for example phosphorus. Herein we present the palladium/copper mediated formation of branched 1-phospha-butadiene derivatives through an unusual alkynylation of a phospha-enyne fragment. Structural and NMR studies provide mechanistic insights into this alkynylation. Furthermore, we disclose a complex cyclisation of the thus obtained 3-yne-1-phosphabutadiene motifs to give highly substituted phosphole derivatives identified by 2D NMR and SC-XRD analysis.

13.
J Lab Physicians ; 14(4): 435-442, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36531546

RESUMO

Introduction Chronic lymphocytic leukemia (CLL) is the commonest hematological malignancy in the West but is relatively uncommon in India. The prognosis of CLL is determined by well-established prognostic markers. CD49d has been emerging as a promising prognostic marker in CLL. CD49d expression in CLL has been found to have an aggressive clinical course, shorter time to first treatment, and poorer prognosis. The aim of this study was to analyze the flow cytometric expression of CD49d in newly diagnosed CLL and to correlate its expression with clinico-hematological parameters. Materials and Methods Twenty-five consecutive patients of CLL, diagnosed on flow cytometry, were included in the study. Patients on treatment or those with relapse were excluded. The panel for flow cytometry included the routine markers used for CLL diagnosis along with CD49d. The expression of CD49d was correlated with clinico-hematological parameters in all patients. "R" software was used for the statistical analysis. Fisher's exact test and Wilcox test were used to assess the correlation of CD49d to categorical and continuous data, respectively. Results The mean age of the patients was 62.6 ± 12.5 years, and 80% were symptomatic at diagnosis. CD49d expression was found in 44% cases, with a higher proportion being male patients. CD49d and prolymphocyte percentage showed a statistically significant correlation ( p = 0.0007). We found a statistically significant correlation between CD49d expression and lymphadenopathy and splenomegaly with p -values of 0.033 and 0.0472, respectively. CD49d positivity correlated significantly with a higher Rai stage ( p = 0.0196) and intermediate and high-risk cases according to Binet staging ( p = 0.033). Conclusion CD49d expression in the present study correlated with a higher prolymphocyte percentage, lymphadenopathy, splenomegaly, and higher Rai and Binet stages. CD49d expression on flow cytometry was reproducible and easy to interpret.

14.
Inorg Chem ; 61(44): 17515-17526, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36279568

RESUMO

Fe(III) complexes with N-heterocyclic carbene (NHC) ligands belong to the rare examples of Earth-abundant transition metal complexes with long-lived luminescent charge-transfer excited states that enable applications as photosensitizers for charge separation reactions. We report three new hexa-NHC complexes of this class: [Fe(brphtmeimb)2]PF6 (brphtmeimb = [(4-bromophenyl)tris(3-methylimidazol-2-ylidene)borate]-, [Fe(meophtmeimb)2]PF6 (meophtmeimb = [(4-methoxyphenyl)tris(3-methylimidazol-2-ylidene)borate]-, and [Fe(coohphtmeimb)2]PF6 (coohphtmeimb = [(4-carboxyphenyl)tris(3-methylimidazol-2-ylidene)borate]-. These were derived from the parent complex [Fe(phtmeimb)2]PF6 (phtmeimb = [phenyltris(3-methylimidazol-2-ylidene)borate]- by modification with electron-withdrawing and electron-donating substituents, respectively, at the 4-phenyl position of the ligand framework. All three Fe(III) hexa-NHC complexes were characterized by NMR spectroscopy, high-resolution mass spectroscopy, elemental analysis, single crystal X-ray diffraction analysis, electrochemistry, Mößbauer spectroscopy, electronic spectroscopy, magnetic susceptibility measurements, and quantum chemical calculations. Their ligand-to-metal charge-transfer (2LMCT) excited states feature nanosecond lifetimes (1.6-1.7 ns) and sizable emission quantum yields (1.7-1.9%) through spin-allowed transition to the doublet ground state (2GS), completely in line with the parent complex [Fe(phtmeimb)2]PF6 (2.0 ns and 2.1%). The integrity of the favorable excited state characteristics upon substitution of the ligand framework demonstrates the robustness of the scorpionate motif that tolerates modifications in the 4-phenyl position for applications such as the attachment in molecular or hybrid assemblies.

15.
Cureus ; 14(8): e28241, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36158348

RESUMO

INTRODUCTION: Next-generation sequencing (NGS) elucidates the diffuse large B-cell lymphoma (DLBCL) genetic characteristics by finding recurrent and novel somatic mutations. This observational study attempted to create an NGS panel with a focus on identifying novel somatic mutations which could have potential clinical and therapeutic implications. This panel was created to look for mutations in 133 genes chosen on basis of a literature review and it was used to sequence the tumor DNA of 20 DLBCL patients after a centralized histopathologic review. METHODS: The study included 20 patients having DLBCL. The quality and quantity of tumor cells were accessed by H&E staining and correlated with histopathology and Immunohistochemistry (IHC) status. Patients were grouped as ABC (activated B-cell), PMBL (primary mediastinal large B-cell lymphoma), and other or unclassified subtypes. The lymphoma panel of 133 was designed on targeted sequencing of multiple genes for the coding regions through NGS. The libraries were prepared and sequenced using the Illumina platform. The alignment of obtained sequences was performed using Burrows-Wheeler Aligner and identification of somatic mutations was done using LoFreq (version 2) variant caller. The mutations were annotated using an annotation pipeline (VariMAT). Previously published literature and databases were used for the annotation of clinically relevant mutations. The common variants were filtered for reporting based on the presence in various population databases (1000G, ExAC, EVS, 1000Japanese, dbSNP, UK10K, MedVarDb). A custom read-depth-based algorithm was used to determine CNV (Copy Number Variants) from targeted sequencing experiments. Rare CNVs were detected using a comparison of the test data read-depths with the matched reference dataset. Reportable mutations were prioritized and prepared based on AMP-ASCO-CAP (Association for Molecular Pathology-American Society of Clinical Oncology-College of American Pathologists), WHO guidelines, and also based on annotation metrics from OncoMD (a knowledge base of genomic alterations). RESULTS: The informativity of the panel was 95 percent. NOTCH 1 was the most frequently mutated gene in 16.1% of patients followed by 12.9% who had ARID1A mutations. MYD88 and TP53 mutations were detected in 9.6% of the patient while 6.4% of patients had CSF3R mutations. NOTCH 1 and TP 53 are the most frequently reported gene in the middle age group (40-60). Mutation in MYD88 is reported in every age group. MYD88 (51%) is the most common mutation in ABC subtypes of DLBCL, followed by NOTCH 1 (44%) and SOCS 1 (33%) according to our findings. NOTCH 1 mutations are frequent in ABC and PMBL subtypes. Closer investigation reveals missense mutation is the most frequent mutation observed in the total cohort targeting 68.4% followed by frameshift deletion reported in 26.3%. Six novel variants have been discovered in this study. CONCLUSIONS: This study demonstrates the high yield of information in DLBCL using the NGS Lymphoma panel. Results also highlight the molecular heterogeneity of DLBCL subtypes which indicates the need for further studies to make the results of the NGS more clinically relevant.

17.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443487

RESUMO

Acute kidney injury (AKI) is a frequently encountered outcome in critically ill patients, accounting for increased mortality. Neutrophil gelatinase associated lipocalin (NGAL) has been of paramount importance as a novel biomarker of AKI. This study is an attempt to assess the use of NGAL in critically ill patients so that timely interventions can be done to reduce morbidity and mortality in such patients. MATERIAL: A prospective observational study was conducted at SRN Hospital, Prayagraj from August 1st 2020 to March 15th 2021, which included only critically ill patients with SOFA score>1 and requiring ICU admission. Patients of known renal diseases were excluded from the study. Blood as well as urinary samples for NGAL and other laboratory parameters were collected within 8 hours of admission. Patients who developed renal dysfunction were noted as our cases and the others were noted as controls. OBSERVATION: The study was done on 125 patients, out of which 67 developed AKI while 58 did not develop AKI. Higher mortality was seen in patients with higher stage of AKI (P- 0.011). The cutoff of serum and urinary NGAL for predicting AKI were >42.3 ng/mL, >40.5 ng/mL respectively (P value <0.001). Hazard Ratio for all cause mortality of raised serum and urinary NGAL was 2.0062 (p value- 0.0001, 95% CI-1.0031 to 1.0092) and 2.0046 (p value-0.0035, 95% CI-1.0015 to 1.0078) respectively. Serum and urinary neutrophil gelatinase associated lipocalin at values >91 and >131 respectively were found to predict requirement of hemodialysis (p value<0.001). CONCLUSION: A single measurement of NGAL at the time of admission had good predictive ability for AKI. Higher values of NGAL were associated with staging of AKI and thus, correlated with need of hemodialysis. Furthermore, mortality was found to be associated with development of AKI and raised NGAL. Thus, NGAL maybe used to assess the prognosis of ICU patients so that patients at high risk may be managed aggressively, thus reducing mortality.


Assuntos
Injúria Renal Aguda , Estado Terminal , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Biomarcadores , Feminino , Humanos , Lipocalina-2/urina , Masculino , Prognóstico
18.
Indian Heart J ; 74(3): 249-250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35331722

RESUMO

Our study aims to evaluate the role of neutrophil gelatinase associated lipocalin (NGAL) as an early surrogate marker in predicting acute kidney injury (AKI) and mortality in cardiac ICU patients. The study was conducted at SRN Hospital, excluding those with known renal diseases. Out of 152 patients, 56 developed AKI (cases) and 96 were our controls. Higher NGAL was associated with increased mortality rates (P = 0.0201 and 0.0255 for serum and urinary NGAL respectively). Our study concluded that NGAL measurement at admission may be a boon in improving the outcome of cardiac ICU patients.


Assuntos
Injúria Renal Aguda , Cardiopatias , Lipocalina-2 , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Biomarcadores/sangue , Biomarcadores/urina , Cardiopatias/sangue , Cardiopatias/complicações , Cardiopatias/urina , Humanos , Unidades de Terapia Intensiva , Lipocalina-2/sangue , Lipocalina-2/urina , Prognóstico , Estudos Prospectivos
19.
J Nat Prod ; 84(12): 3080-3089, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34802242

RESUMO

Five new cyclohexene derivatives, dipandensin A and B (1 and 2) and pandensenols A-C (3-5), and 16 known secondary metabolites (6-21) were isolated from the methanol-soluble extracts of the stem and root barks of Uvaria pandensis. The structures were characterized by NMR spectroscopic and mass spectrometric analyses, and that of 6-methoxyzeylenol (6) was further confirmed by single-crystal X-ray crystallography, which also established its absolute configuration. The isolated metabolites were evaluated for antibacterial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis and the Gram-negative bacteria Enterococcus raffinosus, Escherichia coli, Paraburkholderia caledonica, Pectobacterium carotovorum, and Pseudomonas putida, as well as for cytotoxicity against the MCF-7 human breast cancer cell line. A mixture of uvaretin (20) and isouvaretin (21) exhibited significant antibacterial activity against B. subtilis (EC50 8.7 µM) and S. epidermidis (IC50 7.9 µM). (8'α,9'ß-Dihydroxy)-3-farnesylindole (12) showed strong inhibitory activity (EC50 9.8 µM) against B. subtilis, comparable to the clinical reference ampicillin (EC50 17.9 µM). None of the compounds showed relevant cytotoxicity against the MCF-7 human breast cancer cell line.


Assuntos
Cicloexenos/química , Oxigênio/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Caules de Planta/química , Uvaria/química , Cristalografia por Raios X/métodos , Cicloexenos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Células MCF-7 , Testes de Sensibilidade Microbiana , Extratos Vegetais/química
20.
Chemosphere ; 282: 131062, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34102492

RESUMO

Carbon nanoparticles (CNP) were synthesized through flame deposition method from a sustainable corn oil precursor. The morphology, particle size, surface chemistry, thermal stability, and zeta potential of the CNP were characterized. The batch adsorption of a cationic dye, methylene blue (MB), by the CNP at various concentrations, pH, and temperatures was evaluated to investigate the CNP's efficacy in industrial wastewater treatment applications. Results revealed the excellent adsorption of MB onto the CNP. The experimental data were then fitted into isotherm models, kinetic models, and thermodynamic models, and the model parameters, constants, Gibb free energy, enthalpy, and entropy were calculated and discussed. Hydrogen bonding and strong electrostatic interaction were the main adsorption mechanism for MB adsorption by the CNP. The CNP exhibited a maximum adsorption capacity of 138.89 mg/g, indicating superior adsorption of MB dye without the need for any further purification and activation steps. The adsorption efficiency did not compromise as the solution temperature increased up to 60 °C, and it can further be enhanced under alkaline conditions. To simulate the practical and industrial use of the developed CNP in textile effluent treatment, successful experiments were conducted in continuous flow adsorption by allowing concentrated MB solution to flow through a designed fixed bed purification system with a CNP filter bed.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Adsorção , Carbono , Óleo de Milho , Concentração de Íons de Hidrogênio , Cinética , Azul de Metileno , Termodinâmica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA