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1.
J Pharm Bioallied Sci ; 16(Suppl 1): S707-S710, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595451

ABSTRACT

Mini-screws, also known as temporary anchorage devices (TADs), offer enhanced control and versatility in orthodontic treatment by providing stable anchorage points. This clinical study aims to evaluate the effectiveness of mini-screw-supported molar intrusion in orthodontic practice. For this clinical study, a cohort of 40 orthodontic patients with various malocclusions requiring molar intrusion as part of their treatment plan was recruited. The age range of the participants spanned from 14 to 35 years, representing a diverse patient population. The intervention involved the implementation of mini-screw-supported molar intrusion on one side of the maxillary arch in each patient. To achieve this, temporary mini-screws were strategically placed, and a combination of orthodontic forces and mini-screw anchorage was employed to intrude the molars. The primary outcome measure for this study was the amount of molar intrusion achieved, which was quantified in millimeters from the initial evaluation to the final visit. Additionally, the duration of treatment required to achieve the desired molar intrusion was recorded in months. The results of this clinical study demonstrated that mini-screw-supported molar intrusion was an effective and safe orthodontic technique. On average, a significant mean molar intrusion amount of 4.8 mm (standard deviation [SD] ± 0.6) was achieved with the mini-screw-supported approach. Furthermore, the treatment duration required to attain the desired molar intrusion was relatively short, with a mean of 6.2 months (SD ± 1.1). In conclusion, this clinical study provides evidence that mini-screw-supported molar intrusion is an effective and safe approach in orthodontic practice. It offers orthodontists the advantage of enhanced control and predictability in molar intrusion procedures.

2.
J Perinatol ; 44(5): 612-627, 2024 May.
Article in English | MEDLINE | ID: mdl-38225373

ABSTRACT

Freeze-drying (FD), or lyophilization, is commonly used to preserve foods. FD offers potential to create a human milk-derived human milk fortifier, and an alternative to freeze-storing human milk. However, processing human milk is known to affect its components. This scoping review explores the effect of FD on the; macronutrient, micronutrient, vitamin, bioactive components, microbes and anti-microbial factors in human milk, and studies where lyophilized human milk has been given to newborn infants. 48 articles were identified after full text review. FD human milk reduces the fat globule size and as well as the quantity of enzymes, vitamin C and immunoglobulin. Common serum electrolyte disturbances have been reported when preterm infants' are fed FD human milk however it appears a promising method to avoid exposure of preterm infants' to cows' milk. Due to limited data, further studies exploring the safety and efficacy of FD human milk in preterm infants are needed.


Subject(s)
Freeze Drying , Infant, Premature , Milk, Human , Humans , Milk, Human/chemistry , Infant, Newborn , Infant Nutritional Physiological Phenomena
3.
Dalton Trans ; 53(7): 3010-3019, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38265230

ABSTRACT

Mitochondrial topisomerase 1 (Top1mt) is critical for mtDNA replication, transcription, and energy production. Here, we investigate the carrier-mediated targeted delivery of the anticancer drug irinotecan into the mitochondria to selectively trap Top1mt covalent complexes (Top1mtcc) and its role in anticancer therapeutics. We have designed a biocompatible mesoporous metal-organic framework (MOF) material, namely MIL-101(Fe), as the drug delivery carrier that selectively localizes inside mitochondria. In contrast to the traditional way of synthesising MOFs, here we have employed a vapour-assisted solvothermal method for the synthesis of MIL-101(Fe) using terephthalic acid as the organic linker and Fe(III) as the metal source. The advantage of this method is that it recycles the excess solvent (DMF) and reduces the amount of washing solvent. We demonstrate that MIL-101(Fe)-encapsulated irinotecan (MIL-Iri) was selectively targeted towards the mitochondria to poison Top1mtcc in a dose-dependent manner and was achieved at a low nanomolar drug concentration. We provide evidence that Top1mtcc generated by MIL-Iri leads to mtDNA damage in human colon and breast cancer cells and plays a significant role in cellular toxicity. Altogether, this study provides evidence for a new and effective strategy in anticancer chemotherapy.


Subject(s)
Metal-Organic Frameworks , Humans , Irinotecan/pharmacology , Ferric Compounds , Drug Carriers , Mitochondria , DNA, Mitochondrial , Solvents
4.
J Colloid Interface Sci ; 658: 415-424, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38118188

ABSTRACT

Water splitting is a long-standing quest to material research for mitigating the global energy crisis. Despite high efficiency shown by several high cost noble metal containing electrocatalysts in the water splitting reaction, scientists are focused on alternate metal-free carbon or polymer based materials with comparable activity to make the process economical. In this article, we have strategically designed a noble metal-free thiadiazole (TDA) and triazine (Trz) linked porous organic polymer (TDA-Trz-POP) having N- and S-rich surface. Powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR), solid state 13C magic angle spinning nuclear magnetic resonance (MAS-NMR) and X-ray photoelectron spectroscopic (XPS) analyses have been performed to predict its probable framework structure. This scrunch paper type TDA-Trz-POP shows an extravagant potential for the hydrogen evolution reaction (HER) with a low overpotential (129.2 mV w.r.t. RHE for 10 mA cm-2 current density) and low Tafel slope (82.1 mV deg-1). Again, this metal-free catalyst shows oxygen evolution reaction (OER) at 410 mV overpotential w.r.t RHE for 10 mA cm-2 current density with a lower Tafel slope of 104.5 mV deg-1. This bifunctional activity was further tested in two electrodes set-up under different pH conditions. The porosity seems to be a blessing in the electrocatalytic performance of this metal-free electrocatalyst material. Further, the mystery behind the activity of both HER and OER has been resolved through the density functional theory (DFT) analysis. This work provides an insight to the material scientists for low cost, metal-free material design for the efficient water splitting reaction.

5.
J Biosci ; 482023.
Article in English | MEDLINE | ID: mdl-37439398

ABSTRACT

Bacterial second messenger signaling often plays an important role in cellular physiology. In this study, we have attempted to understand how c-di-AMP synthesis and degradation are transcriptionally regulated in Mycobacterium smegmatis. We found that although a c-di-AMP synthesis gene, disA, exists in a multi-gene operon, a sub-operon promoter arrangement facilitates disA gene expression under normal conditions to maintain intracellular c-di-AMP concentration and is induced further during certain stress adaptations. Individual gene-specific promoters also play a key role under various genotoxic stress conditions to shut down c-di-AMP synthesis, which could otherwise be detrimental for cells. Further, we learned that a high c-di-AMP concentration plays a role in the autoregulation of the disA promoter to limit intracellular c-di-AMP concentration. This study was helpful to understand how c-di-AMP synthesis is regulated under normal and stress conditions linked to its physiological relevance in M. smegmatis.


Subject(s)
Bacterial Proteins , Mycobacterium smegmatis , Mycobacterium smegmatis/genetics , Mycobacterium smegmatis/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Homeostasis/genetics , Operon/genetics , Gene Expression Regulation, Bacterial
6.
Nano Lett ; 23(14): 6602-6609, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37449842

ABSTRACT

Nontrivial polarization textures have been demonstrated in ferroelectric/dielectric superlattices, where the electrostatic, elastic, and different gradient energies compete in a delicate balance. When PbTiO3/SrTiO3 superlattices are grown on DyScO3, the coexistence of ferroelectric domains and vortex structure is observed for n = 12-20 unit cells. Here, we report an approach to achieve single-phase vortex structures in superlattices by controlling the epitaxial strain using Sr1.04Al0.12Ga0.35Ta0.50O3 substrates. The domain width follows Kittel's law with the thickness of the ferroelectric PbTiO3 layers. A phase transition from vortex to a disordered phase with temperature is characterized by the correlation length. Resonant soft X-ray diffraction circular dichroism at the titanium L-edge reveals enhanced chirality with the thickness of the ferroelectric layer. These results are supported by second-principles simulations, which demonstrate that the integrated helicity increases with n. The stabilization of chiral single-phase polar vortices in ferroelectric/dielectric superlattices can enable novel optoelectronic devices with enhanced ferroelectric-light interaction.

7.
ACS Omega ; 8(23): 20513-20523, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37323400

ABSTRACT

Hyperphosphorylated nucleotide (p)ppGpp, synthesized by Rel protein, regulates the stringent response pathway responsible for biofilm and persister cell growth in mycobacteria. The discovery of vitamin C as an inhibitor of Rel protein activities raises the prospect of tetrone lactones to prevent such pathways. The closely related isotetrone lactone derivatives are identified herein as inhibitors of the above processes in a mycobacterium. Synthesis and biochemical evaluations show that an isotetrone possessing phenyl substituent at C-4 inhibit the biofilm formation at 400 µg mL-1, 84 h post-exposure, followed by moderate inhibition by the isotetrone possessing the p-hydroxyphenyl substituent. The latter isotetrone inhibits the growth of persister cells at 400 µg mL-1 f.c. when monitored for 2 weeks, under PBS starvation. Isotetrones also potentiate the inhibition of antibiotic-tolerant regrowth of cells by ciprofloxacin (0.75 µg mL-1) and thus act as bioenhancers. Molecular dynamics studies show that isotetrone derivatives bind to the RelMsm protein more efficiently than vitamin C at a binding site possessing serine, threonine, lysine, and arginine.

8.
Heliyon ; 9(5): e15686, 2023 May.
Article in English | MEDLINE | ID: mdl-37305508

ABSTRACT

Cyclic-di-AMP (c-di-AMP) is an important secondary messenger molecule that plays a critical role in monitoring several important cellular processes, especially in several Gram-positive bacteria. In this study, we seek to unravel the physiological significance of the molecule c-di-AMP in Mycobacterium smegmatis under different conditions, using strains with altered c-di-AMP levels: c-di-AMP null mutant (ΔdisA) and a c-di-AMP over-expression mutant (Δpde). Our thorough analysis of the mutants revealed that the intracellular concentration of c-di-AMP could determine many basic phenotypes such as colony architecture, cell shape, cell size, membrane permeability etc. Additionally, it was shown to play a significant role in multiple stress adaptation pathways in the case of different DNA and membrane stresses. Our study also revealed how the biofilm phenotypes of M. smegmatis cells are altered with high intracellular c-di-AMP concentration. Next, we checked how c-di-AMP contributes to antibiotic resistance or susceptibility characteristics of M. smegmatis, which was followed by a detailed transcriptome profile analysis to reveal key genes and pathways such as translation, arginine biosynthesis, cell wall and plasma membrane are regulated by c-di-AMP in mycobacteria.

9.
Sci Rep ; 13(1): 9251, 2023 06 07.
Article in English | MEDLINE | ID: mdl-37286718

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) has a high fatality rate, mainly due to its asymptomatic nature until late-stage disease and therefore delayed diagnosis that leads to a lack of timely treatment intervention. Consequently, there is a significant need for better methods to screen populations that are at high risk of developing PDAC. Such advances would result in earlier diagnosis, more treatment options, and ultimately better outcomes for patients. Several recent studies have applied the concept of liquid biopsy, which is the sampling of a biofluid (such as blood plasma) for the presence of disease biomarkers, to develop screening approaches for PDAC; several of these studies have focused on analysis of extracellular vesicles (EVs) and their cargoes. While these studies have identified many potential biomarkers for PDAC that are present within EVs, their application to clinical practice is hindered by the lack of a robust, reproducible method for EV isolation and analysis that is amenable to a clinical setting. Our previous research has shown that the Vn96 synthetic peptide is indeed a robust and reproducible method for EV isolation that has the potential to be used in a clinical setting. We have therefore chosen to investigate the utility of the Vn96 synthetic peptide for this isolation of EVs from human plasma and the subsequent detection of small RNA biomarkers of PDAC by Next-generation sequencing (NGS) analysis. We find that analysis of small RNA from Vn96-isolated EVs permits the discrimination of PDAC patients from non-affected individuals. Moreover, analyses of all small RNA species, miRNAs, and lncRNA fragments are most effective at segregating PDAC patients from non-affected individuals. Several of the identified small RNA biomarkers have been previously associated with and/or characterized in PDAC, indicating the validity of our findings, whereas other identified small RNA biomarkers may have novel roles in PDAC or cancer in general. Overall, our results provide a basis for a clinically-amendable detection and/or screening strategy for PDAC using a liquid biopsy approach that relies on Vn96-mediated isolation of EVs from plasma.


Subject(s)
Carcinoma, Pancreatic Ductal , Extracellular Vesicles , MicroRNAs , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Extracellular Vesicles/genetics , Extracellular Vesicles/pathology , MicroRNAs/genetics , Peptides/genetics , Sequence Analysis, RNA , Biomarkers, Tumor/genetics , Pancreatic Neoplasms
10.
Viruses ; 15(6)2023 05 31.
Article in English | MEDLINE | ID: mdl-37376610

ABSTRACT

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Pregnancy , Chlorocebus aethiops , Infant, Newborn , Animals , Female , Humans , COVID-19/diagnosis , SARS-CoV-2 , Placenta , Vero Cells , Trophoblasts , Pregnancy Complications, Infectious/diagnosis , Infectious Disease Transmission, Vertical
11.
Front Bioinform ; 3: 1127661, 2023.
Article in English | MEDLINE | ID: mdl-37252342

ABSTRACT

RNA sequencing analysis is an important field in the study of extracellular vesicles (EVs), as these particles contain a variety of RNA species that may have diagnostic, prognostic and predictive value. Many of the bioinformatics tools currently used to analyze EV cargo rely on third-party annotations. Recently, analysis of unannotated expressed RNAs has become of interest, since these may provide complementary information to traditional annotated biomarkers or may help refine biological signatures used in machine learning by including unknown regions. Here we perform a comparative analysis of annotation-free and classical read-summarization tools for the analysis of RNA sequencing data generated for EVs isolated from persons with amyotrophic lateral sclerosis (ALS) and healthy donors. Differential expression analysis and digital-droplet PCR validation of unannotated RNAs also confirmed their existence and demonstrates the usefulness of including such potential biomarkers in transcriptome analysis. We show that find-then-annotate methods perform similarly to standard tools for the analysis of known features, and can also identify unannotated expressed RNAs, two of which were validated as overexpressed in ALS samples. We demonstrate that these tools can therefore be used for a stand-alone analysis or easily integrated into current workflows and may be useful for re-analysis as annotations can be integrated post hoc.

12.
Langmuir ; 39(11): 4071-4081, 2023 Mar 21.
Article in English | MEDLINE | ID: mdl-36905363

ABSTRACT

Exploring a covalent organic framework (COF) material as an efficient metal-free photocatalyst and as an adsorbent for the removal of pollutants from contaminated water is very challenging in the context of sustainable chemistry. Herein, we report a new porous crystalline COF, C6-TRZ-TPA COF, via segregation of donor-acceptor moieties through the extended Schiff base condensation between tris(4-formylphenyl)amine and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)trianiline. This COF displayed a Brunauer-Emmett-Teller (BET) surface area of 1058 m2 g-1 with a pore volume of 0.73 cc g-1. Again, extended π-conjugation, the presence of heteroatoms throughout the framework, and a narrow band gap of 2.2 eV, all these features collectively work for the environmental remediation in two different perspectives: it could harness solar energy for environmental clean-up, where the COF has been explored as a robust metal-free photocatalyst for wastewater treatment and as an adsorbent for iodine capture. In our endeavor of wastewater treatment, we have conducted the photodegradation of rose bengal (RB) and methylene blue (MB) as model pollutants since these are extremely toxic, are health hazard, and bioaccumulative in nature. The catalyst C6-TRZ-TPA COF showed a very high catalytic efficiency of 99% towards the degradation of 250 parts per million (ppm) of RB solution in 80 min under visible light irradiation with the rate constant of 0.05 min-1. Further, C6-TRZ-TPA COF is found to be an excellent adsorbent as it efficiently adsorbed radioactive iodine from its solution as well as from the vapor phase. The material exhibits a very rapid iodine capturing tendency with an outstanding iodine vapor uptake capacity of 4832 mg g-1.

13.
BMC Cancer ; 23(1): 78, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36690978

ABSTRACT

BACKGROUND: Incidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer. METHODS: The Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2-/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates. RESULTS: 27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35-12.33) and 201.3 (95% CI: 198.05-204.50), respectively, per 100 person-years. HER2-/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). With HER2-/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low. CONCLUSIONS: This study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients' tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.


Subject(s)
Antineoplastic Agents , Brain Neoplasms , Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , United States , Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Electronic Health Records , Retrospective Studies , Antineoplastic Agents/therapeutic use , ErbB Receptors/therapeutic use , Brain Neoplasms/secondary , Seizures/drug therapy , Receptor, ErbB-2/therapeutic use
14.
J Chem Phys ; 157(19): 194905, 2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36414451

ABSTRACT

We have studied the persistence probability p(t) of an active Brownian particle with shape asymmetry in two dimensions. The persistence probability is defined as the probability of a stochastic variable that has not changed its sign in a given fixed time interval. We have investigated two cases: (1) diffusion of a free active particle and (2) that of a harmonically trapped particle. In our earlier work, by Ghosh et al. [J. Chem. Phys. 152, 174901 (2020)], we had shown that p(t) can be used to determine the translational and rotational diffusion constant of an asymmetrically shaped particle. The method has the advantage that the measurement of the rotational motion of the anisotropic particle is not required. In this paper, we extend the study to an active anisotropic particle and show how the persistence probability of an anisotropic particle is modified in the presence of a propulsion velocity. Furthermore, we validate our analytical expression against the measured persistence probability from the numerical simulations of single particle Langevin dynamics and test whether the method proposed in our earlier work can help distinguish between active and passive anisotropic particles.

16.
ACS Appl Mater Interfaces ; 14(33): 37699-37708, 2022 Aug 24.
Article in English | MEDLINE | ID: mdl-35960025

ABSTRACT

Designing an efficient catalyst for a sustainable photoelectrochemical water oxidation reaction is very challenging in the context of renewable energy research. Here, we have introduced a new semiconducting porous zinc-thiolate framework via successful stitching of an "N" donor linker with a triazine-based tristhiolate secondary building unit in the overall architecture. The introduction of both linker and tristhiolate ligand synergistically modifies the architecture by making it a rigid, crystalline, three-dimensional, thermally stable, and porous framework. Our novel zinc-thiolate framework is used as an n-type semiconductor as revealed from the solid-state UV-vis DRS spectroscopic analysis, ac and dc conductivity analysis, and Mott-Schottky plot. This n-type semiconductor-based zinc-thiolate framework is utilized in the photoelectrochemical water oxidation reaction. It displayed a very high efficiency for a visible-light-driven oxygen evolution reaction (OER) in a KOH medium using standard Ag/AgCl as the reference electrode. The superiority of this material was further revealed from the low onset potential (0.822 mV vs RHE), high photocurrent density (0.204 mA cm-2), good stability, and high O2 evolution rate (77 µmol g-1 of oxygen evolution within 2 h), and a good efficiency (ABPE 0.42%, IPCE 29.6% and APCE 34.5%). Furthermore, the porosity in the overall framework seems to be a blessing to the photoelectrochemical performance due to better mass diffusion of the electrolyte. A detailed mechanism for the OER reaction was analyzed through density functional theory analysis suggesting the potential future of this Zn-thiolate framework for achieving a high efficiency in the sustainable water oxidation reaction.

17.
Angew Chem Int Ed Engl ; 61(40): e202207384, 2022 10 04.
Article in English | MEDLINE | ID: mdl-35993443

ABSTRACT

Human telomeric G-quadruplex DNA structures are attractive anticancer drug targets, but the target's polymorphism complicates the drug design: different ligands prefer different folds, and very few complexes have been solved at high resolution. Here we report that Phen-DC3 , one of the most prominent G-quadruplex ligands in terms of high binding affinity and selectivity, causes dTAGGG(TTAGGG)3 to completely change its fold in KCl solution from a hybrid-1 to an antiparallel chair-type structure, wherein the ligand intercalates between a two-quartet unit and a pseudo-quartet, thereby ejecting one potassium ion. This unprecedented high-resolution NMR structure shows for the first time a true ligand intercalation into an intramolecular G-quadruplex.


Subject(s)
Antineoplastic Agents , G-Quadruplexes , DNA/chemistry , Humans , Ligands , Potassium/chemistry , Telomere
18.
Sci Rep ; 12(1): 13127, 2022 07 30.
Article in English | MEDLINE | ID: mdl-35907936

ABSTRACT

In this study, we probe the role of secondary messenger c-di-AMP in drug tolerance, which includes both persister and resistant mutant characterization of Mycobacterium smegmatis. Specifically, with the use of c-di-AMP null and overproducing mutants, we showed how c-di-AMP plays a significant role in resistance mutagenesis against antibiotics with different mechanisms of action. We elucidated the specific molecular mechanism linking the elevated intracellular c-di-AMP level and high mutant generation and highlighted the significance of non-homology-based DNA repair. Further investigation enabled us to identify the unique mutational landscape of target and non-target mutation categories linked to intracellular c-di-AMP levels. Overall fitness cost of unique target mutations was estimated in different strain backgrounds, and then we showed the critical role of c-di-AMP in driving epistatic interactions between resistance genes, resulting in the evolution of multi-drug tolerance. Finally, we identified the role of c-di-AMP in persister cells regrowth and mutant enrichment upon cessation of antibiotic treatment.


Subject(s)
Anti-Bacterial Agents , Mycobacterium smegmatis , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Dinucleoside Phosphates , Drug Tolerance , Mycobacterium smegmatis/genetics , Phenotype
19.
Micromachines (Basel) ; 13(5)2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35630197

ABSTRACT

Extracellular vesicles (EVs) are a group of communication organelles enclosed by a phospholipid bilayer, secreted by all types of cells. The size of these vesicles ranges from 30 to 1000 nm, and they contain a myriad of compounds such as RNA, DNA, proteins, and lipids from their origin cells, offering a good source of biomarkers. Exosomes (30 to 100 nm) are a subset of EVs, and their importance in future medicine is beyond any doubt. However, the lack of efficient isolation and detection techniques hinders their practical applications as biomarkers. Versatile and cutting-edge platforms are required to detect and isolate exosomes selectively for further clinical analysis. This review paper focuses on lab-on-chip devices for capturing, detecting, and isolating extracellular vesicles. The first part of the paper discusses the main characteristics of different cell-derived vesicles, EV functions, and their clinical applications. In the second part, various microfluidic platforms suitable for the isolation and detection of exosomes are described, and their performance in terms of yield, sensitivity, and time of analysis is discussed.

20.
J Perinatol ; 42(10): 1368-1373, 2022 10.
Article in English | MEDLINE | ID: mdl-35508716

ABSTRACT

OBJECTIVE: To evaluate impact of a quality improvement (QI) outreach education on incidence of acute brain injury in transported premature neonates. STUDY DESIGN: Neonates born at <33 weeks gestation outside the tertiary center were included. The QI intervention was a combination of neuroprotection care bundle, in-person visits, and communication system improvement. Descriptive and regression (adjusting for Gestational Age, Birth Weight, Gender, and antenatal steroids, Mode of delivery, Apgars at 5 minutes, Prophylactic indomethacin, PDA, and Inotropes use) analyses were performed. The primary outcome was a composite of death and/or severe brain injury on cranial ultrasound using a validated classification. RESULTS: 181 neonates studied (93 before and 88 after). The rate and adjusted odds of death and/or severe brain injury reduced significantly post intervention (30% vs 15%) and (AOR 0.36, 95%CI, 0.15-0.85, P = 0.02) respectively. CONCLUSION: Implementation of outreach education targeting neuroprotection can reduce acute brain injury in transported premature neonates.


Subject(s)
Brain Injuries , Premature Birth , Brain Injuries/epidemiology , Brain Injuries/prevention & control , Female , Gestational Age , Humans , Incidence , Indomethacin , Infant, Newborn , Pregnancy , Quality Improvement , Retrospective Studies , Steroids
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