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1.
J Am Chem Soc ; 146(37): 25403-25408, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39248434

RESUMEN

Porphyrin dyes with strong push-pull type intramolecular charge transfer (ICT) character and broad absorption across the visible spectrum are reported. This combination of properties has been achieved by functionalizing the periphery of hypervalent and highly electron-deficient phosphorus(V) and antimony(V) centered porphyrins with electron-rich triphenylamine (TPA) groups. As a result of the large difference in electronegativity between the porphyrin ring and the peripheral groups, their absorption profiles show several strong charge transfer transitions, which in addition to the porphyrin-centered π → π* transitions, make them panchromatic black dyes with high absorption coefficients between 200 and 800 nm. Time-resolved optical and electron paramagnetic resonance (EPR) studies show that the lowest triplet state also has ICT character and is populated by spin-orbit coupled intersystem crossing.

2.
Int J Biol Macromol ; 279(Pt 2): 135247, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39222787

RESUMEN

Arabinoxylan (AX) from cereals and millets have garnered attention due to the myriad of their bioactivities. Pearl millet (Pennisetum glaucum) bran, an underexplored milling by-product was used to extract AX (PMAX) by optimized alkali-assisted extraction using Response Surface Methodology and Central Composite Design, achieving a yield of 15.96 ± 0.39 % (w/w) under optimal conditions (0.57 M NaOH, 1:17 g/mL solid-to-liquid ratio, 60 °C, 4 h). Structural analysis revealed that PMAX was primarily composed of arabinose, xylose, glucose, galactose, and mannose (molar ratio 45.1:36.1:10.4:7.1:1.8), with a highly substituted (1 â†’ 4)-linked ß-D-xylopyranose backbone and a molecular weight of 794.88 kDa. PMAX displayed a significant reducing power of 0.617, metal chelating activity of 51.72 %, and DPPH, and ABTS radical scavenging activities (64.43 and 75.4 %, respectively at 5 mg/mL). It also demonstrated anti-glycation effects by inhibiting fructosamine (52.5 %), protein carbonyl (53.6 %), and total advanced glycation end products (77.0 %) formation, and reduced protein oxidation products such as dityrosine (84.7 %), kynurenine (80.2 %), and N'-formyl-kynurenine (50.0 %) at 5 mg/mL. PMAX induced the growth of Lactobacillus spp. in vitro and modulate gut microbiota in male Wistar rats by increasing Bacteroidetes and decreasing Firmicutes. These results provide a basis for further research on pearl millet arabinoxylan and its possible nutraceutical application.

3.
Cell Physiol Biochem ; 58(4): 418-430, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39172137

RESUMEN

BACKGROUND/AIMS: After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS). While re-purposing drugs that enhance marrow repopulation treats H-ARS, no mitigator protects GI tract. METHODS: We recently reported anti-ceramide 6B5 single-chain variable fragment (scFv) pre-treatment abrogates ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells, preventing GI-ARS lethality in C57B/L6J mice. Here, with US Department of Defense support, we provide evidence that humanized anti-ceramide scFv (CX-01) is a promising prophylactic MRC for first responders, who risk exposure upon entering a radiation-contaminated site. RESULTS: CX-01, when delivered up to 90 min before irradiation, is highly-effective in preventing small intestinal endothelial apoptosis in mice and lethality in both sexes. Unexpectedly, females require an ~2-fold higher CX-01 dose than males for full protection. CX-01 is effective subcutaneously and intramuscularly, a property critical for battlefield use. Increasing the maximally-effective dose 5-fold does not extend duration of bioeffectiveness. CONCLUSION: While CX-01 prevents GI-ARS lethality, structural modification to extend half-life may be necessary to optimize first responder prophylaxis.


Asunto(s)
Apoptosis , Ceramidas , Ratones Endogámicos C57BL , Anticuerpos de Cadena Única , Animales , Anticuerpos de Cadena Única/inmunología , Femenino , Ratones , Masculino , Ceramidas/metabolismo , Apoptosis/efectos de los fármacos , Síndrome de Radiación Aguda/patología , Síndrome de Radiación Aguda/tratamiento farmacológico , Síndrome de Radiación Aguda/prevención & control , Humanos , Armas Nucleares , Protectores contra Radiación/farmacología , Protectores contra Radiación/uso terapéutico , Intestino Delgado/patología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/efectos de la radiación
4.
ACS Omega ; 9(21): 22892-22902, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38826543

RESUMEN

Modulation of intramolecular charge transfer (ICT) has been tested in two antimony(V) porphyrins, SbT(DMP)P(OMe)2·PF6 and SbT(DMP)P(OTFE)2·PF6, where the meso-positions are occupied by 3,5-dimethoxyphenyl (DMP), and the axial positions are linked with either methoxy (OMe) or trifluoroethoxy (OTFE) units, respectively. The presence of the Sb(+5) ion makes the porphyrin center electron poor. Under this situation, placing electron-rich units in the meso-position creates a condition for push-pull type ICT in the SbT(DMP)P(OMe)2·PF6. Remarkably, it is shown that the ICT character can be further enhanced in SbT(DMP)P(OTFE)2·PF6 with the help of electron-withdrawing TFE units in the axial position, which makes the porphyrin center even more electron scarce. The steady-state and transient studies as well as solvatochromism studies establish the ICT in SbT(DMP)P(OMe)2·PF6 and SbT(DMP)P(OTFE)2·PF6, and the strength of the ICT can be modulated by exploiting the structural properties of antimony(V) porphyrin. The existence of ICT is further supported by density functional theory calculations. The transient studies show that upon excitation of these porphyrin, their charge-transfer states convert to a full charger-separated states with appreciable lifetimes.

5.
J Mater Chem B ; 12(24): 5982-5993, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38809161

RESUMEN

This work aimed to manufacture Ti-28.5Nb and Ti-40.0Nb (wt%) alloys in situ via selective laser melting (SLM) from Ti and Nb elemental powders. X-ray diffraction analysis revealed complete ß-phase (cubic) in Ti-40.0Nb and a mixture of (α'' orthorhombic + ß cubic) phases in Ti-28.5Nb were formed, whereas few of the Nb particles remained only partially fused during manufacturing. The fraction of partially melted Nb particles was determined as ∼2 and ∼18% in Ti-28.5Nb and Ti-40Nb, respectively. Mechanical characterization revealed higher hardness and more strength in Ti-28.5Nb than in Ti-40.0Nb due to the presence of the α'' phase in the former. Tribocorrosion tests reveal a significantly better wear-corrosion resistance for Ti-40.0Nb, as determined from a lower total volume loss in Ti-40.0Nb (∼2 × 10-4 mm-3) than in Ti-28.5Nb (∼13 × 10-2 mm-3). The lower volume loss and better corrosion resistance behavior are attributed to the ß phase, which was dominant in Ti-40.0Nb. Cell studies reveal no toxicity for up to 7 days. Both the alloys were better at supporting cell proliferation than wrought Ti6Al4V. This study presents a route to preparing Ti-Nb alloys in situ by SLM that are promising candidates for biomedical applications.


Asunto(s)
Aleaciones , Rayos Láser , Niobio , Titanio , Aleaciones/química , Niobio/química , Titanio/química , Ensayo de Materiales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Humanos , Animales , Propiedades de Superficie , Proliferación Celular/efectos de los fármacos , Ratones
6.
Gene ; 924: 148552, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-38734189

RESUMEN

Acinetobacter baumannii is an important Gram-negative nosocomial pathogen that causes opportunistic infections and employs different mechanisms to survive in the presence of antibiotics in the host. Nutrient limitation is one of the important defense mechanisms of the mammalian immune system to fight against the colonization of pathogens like A. baumannii. The present study describes an NtrC-type Response Regulator (RR) A1S_1978 involved in modulating the metabolism and cell morphology of A. baumannii via a two-component system. This RR was found to be highly conserved in the Acinetobacter and other important Gram-negative pathogens. Sequence analysis reveals that this RR contains an HTH_8 DNA-binding domain. It is also observed that deletion of this RR resulted in elongated cell phenotype and altered colony morphology of A. baumannii. We showed that the ability of A. baumannii to form biofilm and pellicle is partly abolished upon deletion of this response regulator. We showed that mutant strains lacking RR A1S_1978 have diminished growth in the absence of the nitrogen source. The transcriptome analysis of the A1S_1978 deletion mutant revealed that 253 genes were differentially expressed, including 80 genes that were upregulated by at least 2-fold and 173 genes that were down regulated in the ΔA1S_1978 strain. The transcriptome data showed an association between the A1S_1978 RR and key genes related to various nitrogen and amino acid metabolism processes, which was further confirmed by real time PCR analysis. The deletion of this RR leads to a reduction in persister cell formation against ciprofloxacin antibiotic. Taken together the results of this investigation provide significant evidence that the RR A1S_1978 is a global regulator in A. baumannii.


Asunto(s)
Acinetobacter baumannii , Proteínas Bacterianas , Biopelículas , Regulación Bacteriana de la Expresión Génica , Nitrógeno , Acinetobacter baumannii/metabolismo , Acinetobacter baumannii/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Nitrógeno/metabolismo , Biopelículas/crecimiento & desarrollo
7.
Int J Biol Macromol ; 267(Pt 1): 131419, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38583831

RESUMEN

The booming mushroom industry envisages economic merits, and massive unutilized waste production (∼ 20 %) creates an opportunity for valorization. Chitosan, a bioactive polysaccharide, has drawn immense attention for its invaluable therapeutic potential. Thus, the present study was conducted to extract chitosan from mushroom waste (MCH) for its prebiotic potential. The structural characterization of MCH was carried out using NMR, FTIR, and XRD. The CP/MAS-13CNMR spectrum of MCH appeared at δ 57.67 (C2), 61.19 (C6), 75.39 (C3/C5), 83.53 (C4), 105.13 (C1), 23.69 (CH3), and 174.19 (C = O) ppm. The FTIR showed characteristic peaks at 3361 cm-1, 1582 cm-1, and 1262 cm-1 attributed to -NH stretching, amide II, and amide III bands of MCH. XRD interpretation of MCH exhibited a single strong reflection at 2θ =20.19, which may correspond to the "form-II" polymorph. The extracted MCH (∼ 47 kDa) exhibited varying degrees of deacetylation from 79 to 84 %. The prebiotic activity score of 0.73 to 0.82 was observed for MCH (1 %) when supplemented with probiotic strains (Lactobacillus casei, L. helveticus, L. plantarum, and L. rhamnosus). MCH enhanced the growth of Lactobacillus strains and SCFA's levels, particularly in L. rhamnosus. The MCH also inhibited the growth of pathogenic strains (MIC of 0.125 and 0.25 mg/mL against E. coli and S. aureus, respectively) and enhanced the adhesion efficiency of probiotics (3 to 8 % at 1 % MCH supplementation). L. rhamnosus efficiency was higher against pathogens in the presence of MCH, as indicated by anti-adhesion assays. These findings suggested that extracted polysaccharides from mushroom waste can be used as a prebiotic for ameliorating intestinal dysbiosis.


Asunto(s)
Quitosano , Peso Molecular , Pleurotus , Prebióticos , Pleurotus/química , Quitosano/química , Quitosano/farmacología , Residuos/análisis
8.
Neurosci Lett ; 832: 137792, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38677540

RESUMEN

MicroRNAs (miRNAs) have emerged as critical regulators of post-transcriptional gene expression, impacting various biological processes (development, differentiation, and progression). In medicine, miRNAs are promising diagnostic biomarkers for neurodegenerative diseases, including Parkinson's disease (PD). The current study aims at exploring the role of miRNAs and transcription factors (TFs) in regulating genes-associated with PD. Deploying bioinformatics tools, the study identifies specific miRNAs and TFs involved in PD and their potential connections to the organ-disease junction. Notably, certain miRNAs are found to be highly expressed in brain, than compared to blood. Furthermore, the study explores the expression patterns of PD-related genes in different regions of the brain and attempts to construct complex network of interactions contributing to PD pathogenesis. Additionally, the regulatory relationship of two miRNAs namely hsa-miR-375-3p and hsa-miR-423-3p with TFs are well examined. Overall, the study provides a comprehensive moon-shot view of the molecular aspects of PD and their potential therapeutic targets which could be further used as diagnostic biomarkers in early detection, drug design and development attributing towards precision medicine.


Asunto(s)
MicroARNs , Enfermedad de Parkinson , Factores de Transcripción , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Redes Reguladoras de Genes , Biomarcadores/metabolismo , Encéfalo/metabolismo , Regulación de la Expresión Génica , Biología Computacional/métodos
9.
Obstet Med ; 17(1): 50-52, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38660317

RESUMEN

Gestational diabetes mellitus is a common medical disorder of pregnancy. Diabetic ketoacidosis is a complication that may affect both maternal and perinatal wellbeing adversely. It is rare, most often involving women with type 1 or type 2 diabetes, but occasionally can be seen in gestational diabetes mellitus. Here are two cases of ketoacidosis seemingly triggered by glucose ingestion for the oral glucose tolerance test in previously normoglycemic women, posing a diagnostic and therapeutic challenge. Prevention of such complications must be considered when treating high-risk pregnant women> 40 years of age, pregnant as a result of assisted reproductive techniques. Fasting blood glucose checked before ingestion of the glucose in a selected group of women may be one way of avoiding this complication. This suggestion may put women at risk of prolonged fasting and stretching services. Glucose tolerance test is a diagnostic test, and these cases demonstrate a rare complication.

10.
Indian J Otolaryngol Head Neck Surg ; 76(2): 1522-1525, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38566675

RESUMEN

Benign laryngeal lesions like vocal nodules, vocal polyp, vocal fold cysts are mostly found in patients complaining of change in voice. S/Z ratio has become the most frequently used clinical tool to assess phonatory mechanics. This study shows the pre-treatment and post-treatment comparison of S/Z ratios in patients with benign laryngeal lesions. To evaluate the outcome of microlaryngeal surgery in patients with benign laryngeal lesions using S/Z ratio as an outcome parameter. During this study, 65 patients with complaints of change in voice, with clinical evidence of benign laryngeal lesions underwent microlaryngeal surgery. Improvement in symptoms were measured preoperatively and postoperatively using S/Z ratio. This ratio was calculated by asking the patient to to maximally sustain 'S' and 'Z', repeated thrice. S/Z ratio was calculated by dividing the maximum duration for which /S/ was sustained by the maximum duration for which /Z/ was sustained. A ratio of more than 1.4 suggested a vocal cord disorder. There was statistically significant difference observed in S/Z ratio values, from pre-treatment to 6 months post-treatment, with P value 0.001. Pre and post treatment assessment of patients with benign vocal fold lesions showed significant improvement in S/Z ratio postoperatively. It is the simplest and a reliable objective method of voice assessment and can also be used in assessing the outcome of the treatment.

11.
Indian J Otolaryngol Head Neck Surg ; 76(1): 770-774, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38440456

RESUMEN

The relationship between nasal obstruction and obstructive sleep apnea has raised interest among otolaryngologists since years. There are studies that suggest that surgical correction of nasal obstruction improves sleep quality and reduces symptoms of sleep apnea. This lead to our study to understand the effect of nasal surgery on obstructive sleep apnea hypopnea syndrome (OSAHS). AIM: To assess the effect of nasal surgery in improvement in Obstructive Sleep Apnoea Hypopnoea Syndrome in patients with nasal obstruction by Polysomnography (PSG). MATERIAL AND METHODS: This study included 30 patients with nasal obstruction who underwent septoplasty and/or turbinate reduction procedure with pre and post operative assessment of respiratory distress index (RDI) including apnoea hypopnoea index (AHI), obstructive apnoea index (OAI), Snoring Index (SI) using polysomnography (PSG). RESULT: Nasal correction surgery showed statistically significant improvement (p-value < 0.001) in RDI from 13.66 to 6.66, OAI from 6.34 to 3.18 and Snoring Index from 161.77 to 62.23 as assessed by polysomnography. There was statistically significant improvement in minimal saturation levels (during sleep) and positional sleep apnoea. CONCLUSION: Isolated nasal surgery like septoplasty and/or turbinate reduction improved sleep parameters and alleviated OSA symptoms in patients with static nasal obstruction and obstructive sleep apnoea/hypopnoea syndrome. However, patients with multilevel or dynamic airway obstruction may need further intervention.

12.
Micron ; 180: 103613, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38428322

RESUMEN

Sustainable TiC-Fe-based cermets have been fabricated by adopting an Additive Manufacturing route based on laser powder bed fusion technology (L-PBF). The objective is to produce crack-free cermet components by employing novel multiple laser scanning techniques with variations in laser process parameters. Electron backscatter diffraction analysis (EBSD) was used to study the microstructure and microtexture evolution with variations in laser process parameters. The investigation revealed that adjusting the preheating scan speed (PHS) and melting scan speed (MS) influenced the growth and nucleation of TiC phases. Lowering these speeds resulted in grain coarsening, while higher scan speeds led to grain refinement with larger sub-grain boundaries. Moreover, a high scanning speed increases the degree of dislocation density and internal stress in the fabricated cermet parts. Notably, it is revealed that decreasing the laser scan speed enhanced the proportion of high-angle grain boundaries in the cermet components, signifying an increase in material ductility.

13.
3D Print Addit Manuf ; 11(1): 143-151, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38389669

RESUMEN

Nitinol (NiTi) is well known for its corrosion resistance, shape memory effect, superelasticity, and biocompatibility, whereas Titanium (Ti) is well known for its high specific strength, corrosion resistance, and biocompatibility. The bimetallic joint of NiTi and Ti is required for applications that require tailored properties at different locations within the same component, as well as to increase design flexibility while reducing material costs. However, because of the formation of brittle intermetallic phases, connecting NiTi and Ti is difficult. In the present study, a systematic experimental investigation is carried out to develop NiTi-Ti bimetallic joint using wire arc additive manufacturing (WAAM) for the first time and to evaluate its microstructure, mechanical properties, martensitic transformation, and actuation behavior in the as-built condition. The defect-free joint is obtained through WAAM and microstructural studies indicate the formation of intermetallics at the NiTi-Ti interface leading to higher microhardness values (600 HV). Shape recovery behavior and phase transformation temperature were also enhanced in comparison to NiTi. An improved actuation and bending angle recovery is observed in comparison with NiTi. The present study lays the way for the use of WAAM in the construction of NiTi and Ti bimetallic structures for engineering and medicinal applications.

14.
Eur J Hybrid Imaging ; 7(1): 26, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38036687

RESUMEN

A 60-year-old male patient diagnosed with mucinous adenocarcinoma of lower third of rectum underwent abdominoperineal resection and permanent colostomy followed by adjuvant chemotherapy. Response evaluation with F-18 FDG PET-CT showed a complete metabolic response. After 6 months, CEA levels started increasing and clinically a recurrence was suspected. A restaging FDG PET-CT showed no obvious malignant disease. Patient presented again within a month with complaints of urinary retention and haematuria. CEA levels were further elevated, and Ga-68 FAPI-04 (FAPI) PET-CT was performed. FAPI PET-CT revealed prostatic and seminal vesicle disease involvement. Additionally, an MRI of pelvis was done and fused with FAPI PET for confirmation of prostatic involvement.

15.
J Appl Microbiol ; 134(11)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37951296

RESUMEN

AIM: To evaluate the structure and functions of capsular exopolysaccharide (CPS) from Bifidobacterium breve NCIM 5671. METHODS AND RESULTS: A CPS produced by the probiotic bacteria B. breve NCIM 5671 was isolated and subjected to characterization through GC analysis, which indicated the presence of rhamnose, fucose, galactose, and glucose in a molar ratio of 3:1:5:3. The average molecular weight of the CPS was determined to be ∼8.5 × 105 Da. Further, NMR analysis revealed the probable CPS structure to be composed of major branched tetra- and penta-saccharide units alternately repeating and having both α- and ß-configuration sugar residues. CPS displayed an encouraging prebiotic score for some of the studied probiotic bacteria. Compared to standard inulin, CPS showed better resistance to digestibility against human GI tract in vitro. DPPH, total antioxidant, and ferric reducing assays carried out for CPS displayed decent antioxidant activity too. CONCLUSION: This study indicates that the CPS from B. breve NCIM 5671 has the potential to be utilized as a prebiotic food supplement. It is a high-molecular-weight (∼8.5 × 105 Da) capsular heteropolysaccharide containing rhamnose, fucose, galactose, and glucose.


Asunto(s)
Bifidobacterium breve , Prebióticos , Humanos , Fucosa , Galactosa , Ramnosa , Glucosa
16.
Cureus ; 15(10): e47381, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38022087

RESUMEN

Introduction The earth has experienced significant shifts in climate patterns over the past few years. The main aim of this investigation was to establish the association between the sociodemographic factors on the extent of knowledge, perspectives, and awareness of the urban population in Delhi and the phenomenon of climate change. Materials and methods This study was conducted on 1,200 individuals residing in Delhi, India, who were given a well-organized validated questionnaire to gather data. The relationship between different factors influencing awareness and climate change was evaluated using the chi-square test. Results The investigation's findings revealed that the younger generations exhibited heightened consciousness as a result of the impact of education and social media, both of which possess an exceedingly significant role in the dissemination of awareness. Additional elements that influenced the participants' awareness regarding climate change encompassed their educational attainment, profession, and financial resources, which were noticeably more advantageous for the upper and upper-middle social strata. A majority of the respondents, amounting to 65%, hailed from the middle class, with 61% of them holding degrees. The majority of the respondents were well-informed about climate change, with a predominant percentage falling within the age range of 21-40 years (77%) and over the age of 61 years (73%). Notably, 92% of the respondents belonging to the upper class exhibited awareness of climate change. About 52% of the respondents expressed a moderate level of concern towards climate change. Conclusions The analysis revealed that most individuals possessed knowledge regarding the impact of climate change on their way of life. Consequently, they acknowledged the significance of acquiring a more comprehensive understanding of climate change.

17.
Dalton Trans ; 52(40): 14287-14296, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37791453

RESUMEN

The chemistry of Group 15 porphyrins has been established relatively well among the main-group porphyrins. Thus far phosphorus(III), phosphorus(V), arsenic(III), arsenic(V), antimony(III), antimony(V), and bismuth(III) porphyrins have been reported. Their unique axial-bonding ability, rich redox, and optical properties offer an advantage over other main-group or transition metal porphyrins. They could be excellent candidates for a variety of applications such as solar energy harvesting, molecular electronics, molecular catalysis, and biomedical applications. Despite these unique properties, the Group 15 porphyrins are not exploited at their fullest capacity. Recently, there has been some interest, where the richness of Group 15 porphyrin chemistry was explored for some of the above applications. In this context, this article summarizes recent advances in Group 15 porphyrin chemistry and attempts to unravel the tremendous opportunities of these remarkable porphyrins.

18.
Microbiol Resour Announc ; 12(11): e0022023, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37819106

RESUMEN

Among the species within Acb-complex, Acinetobacter lactucae has not been frequently isolated from clinical settings, unlike Acinetobacter baumannii, which is an important nosocomial pathogen. We report the genomic sequences of A. lactucae strains (PKAL1732 and 1828C) harboring multiple-resistance determinants including metallo-ß-lactamase (bla NDM-1) isolated from immunocompromised patients admitted to a referral hospital in India.

19.
Artículo en Inglés | MEDLINE | ID: mdl-37815783

RESUMEN

PURPOSE: After September 11, 2001, nuclear threat prompted government agencies to develop medical countermeasures to mitigate two syndromes, the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS), both lethal within weeks. While repurposing leukemia drugs that enhance bone marrow repopulation successfully treats H-ARS, no mitigator potentially deliverable under mass casualty conditions preserves the GI tract. We recently reported that anti-ceramide single-chain variable fragment (scFv) mitigates GI-ARS lethality, abrogating ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells. Here, we examine long-term consequences of prevention of acute GI-ARS lethality. METHODS AND MATERIALS: For these studies, C57BL/6J male mice were treated with 15 Gy whole body irradiation, the 90% GI-ARS lethal dose for this mouse strain. RESULTS: Mice irradiated with 15 Gy alone or with 15 Gy + bone marrow transplantation (BMT) or anti-ceramide scFv, succumb to an ARS within 8 to 10 days. Autopsies reveal only mice receiving anti-ceramide scFv at 24 hours post-whole body irradiation display small intestinal rescue. No marrow reconstitution occurs in any group with attendant undetectable circulating blood elements. Mice receiving 15 Gy + BMT + scFv, however, normalize blood counts by day 12, suggesting that scFv also improves marrow reconstitution, a concept for which we provide experimental support. We show that at 14 Gy, the upper limit dose for H-ARS lethality before transition to GI-ARS lethality, anti-ceramide scFv markedly improves marrow take, reducing the quantity of marrow-conferring survival by more than 3-fold. Consistent with these findings, mice receiving 15 Gy + BMT + scFv exhibit prolonged survival. At day 90, before sacrifice, they display normal appearance, behavior, and serum biochemistries, and surprisingly, at full autopsy, near-normal physiology in all 42 tissues examined. CONCLUSIONS: Anti-ceramide scFv mitigates GI-ARS lethality and improves marrow reconstitution rendering prolonged survival with near normal autopsies.

20.
EMBO Mol Med ; 15(11): e17694, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37635627

RESUMEN

Therapies reconstituting autologous antiviral immunocompetence may represent an important prophylaxis and treatment for immunosuppressed individuals. Following hematopoietic cell transplantation (HCT), patients are susceptible to Herpesviridae including cytomegalovirus (CMV). We show in a murine model of HCT that macrophage colony-stimulating factor (M-CSF) promoted rapid antiviral activity and protection from viremia caused by murine CMV. M-CSF given at transplantation stimulated sequential myeloid and natural killer (NK) cell differentiation culminating in increased NK cell numbers, production of granzyme B and interferon-γ. This depended upon M-CSF-induced myelopoiesis leading to IL15Rα-mediated presentation of IL-15 on monocytes, augmented by type I interferons from plasmacytoid dendritic cells. Demonstrating relevance to human HCT, M-CSF induced myelomonocytic IL15Rα expression and numbers of functional NK cells in G-CSF-mobilized hematopoietic stem and progenitor cells. Together, M-CSF-induced myelopoiesis triggered an integrated differentiation of myeloid and NK cells to protect HCT recipients from CMV. Thus, our results identify a rationale for the therapeutic use of M-CSF to rapidly reconstitute antiviral activity in immunocompromised individuals, which may provide a general paradigm to boost innate antiviral immunocompetence using host-directed therapies.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Humanos , Ratones , Animales , Citomegalovirus , Factor Estimulante de Colonias de Macrófagos , Trasplante de Células Madre Hematopoyéticas/métodos , Infecciones por Citomegalovirus/prevención & control , Hematopoyesis , Antivirales/farmacología , Antivirales/uso terapéutico , Diferenciación Celular
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