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1.
Cureus ; 16(4): e58179, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38741848

RESUMEN

The delayed presentation of a 15-year-old female with a complex Grade 4 liver injury and a concurrent Grade 1 renal injury sustained from a fall exemplifies the heightened vulnerability of adolescents to blunt hepatic trauma. Unlike typical presentations where symptoms like abdominal pain and internal bleeding appear immediately, this case emphasises the potential for delayed manifestation, posing unique challenges for diagnosis and management. This case, managed at a leading trauma centre, underscores the distinct challenges compared to adult cases due to adolescents' larger space available for the organ and immature livers. While presenting more management complexity than typical splenic injuries, prompt intervention with emergency laparotomy and hepatic packing proved crucial for the patient's successful outcome. This case emphasises the critical role of early identification, vigilant monitoring, and strict activity restrictions post-operatively for optimal adolescent liver trauma management and serves as a reminder of the spectrum of potential injuries, including bile duct and vascular damage alongside contusions and haematomas.

2.
Int Immunopharmacol ; 134: 112205, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38718659

RESUMEN

Current methods for delivering genes to target tumors face significant challenges, including off-target effects and immune responses against delivery vectors. In this study, we developed a novel approach using messenger RNA (mRNA) to encode IL11RA for local immunotherapy, aiming to harness the immune system to combat tumors. Our research uncovered a compelling correlation between IL11RA expression and CD8 + T cell levels across multiple tumor types, with elevated IL11RA expression correlating with improved overall survival. Examination of the Pan-Cancer Atlas dataset showed a significant reduction in IL11RA expression in various cancer types compared to normal tissue, raising questions about its potential role in tumorigenesis. To achieve efficient in vivo expression of IL11RA, we synthesized two mRNA sequences mimicking the wild-type protein. These mRNA sequences were formulated and capped to ensure effective delivery, resulting in robust expression within tumor sites. Our investigation into IL11RA mRNA therapy demonstrated its effectiveness in controlling tumor growth when administered both intratumorally and intravenously in mouse models. Additionally, IL11RA mRNA treatment significantly stimulated the expansion of CD8 + T cells within tumors, draining lymph nodes, and the spleen. Transcriptome analysis revealed distinct transcriptional patterns associated with T cell functions. Using multiple deconvolution algorithms, we found substantial infiltration of CD8 + T cells following IL11RA mRNA treatment, highlighting its immunomodulatory effects within the tumor microenvironment. In conclusion, IL11RA mRNA therapy presents a promising strategy for tumor regression with potential immunomodulatory effects and clinical implications for improved survival outcomes.

3.
Biometals ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38705945

RESUMEN

With the emergence of drug-resistance, there is a need for novel anti-bacterials or to enhance the efficacy of existing drugs. In this study, Patuletin (PA), a flavanoid was loaded onto Gallic acid modified Zinc oxide nanoparticles (PA-GA-ZnO), and evaluated for antibacterial properties against Gram-positive (Bacillus cereus and Streptococcus pneumoniae) and Gram-negative (Samonella enterica and Escherichia coli) bacteria. Characterization of PA, GA-ZnO and PA-GA-ZnO' nanoparticles was accomplished utilizing fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology analysis through atomic force microscopy. Using bactericidal assays, the results revealed that ZnO conjugation displayed remarkable effects and enhanced Patuletin's effects against both Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentration observed at micromolar concentrations. Cytopathogenicity assays exhibited that the drug-nanoconjugates reduced bacterial-mediated human cell death with minimal side effects to human cells. When tested alone, drug-nanoconjugates tested in this study showed limited toxic effects against human cells in vitro. These are promising findings, but future work is needed to understand the molecular mechanisms of effects of drug-nanoconjugates against bacterial pathogens, in addition to in vivo testing to determine their translational value. This study suggests that Patuletin-loaded nano-formulation (PA-GA-ZnO) may be implicated in a multi-target mechanism that affects both Gram-positive and Gram-negative pathogen cell structures, however this needs to be ascertained in future work.

4.
Eur J Med Chem ; 271: 116440, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38678825

RESUMEN

Antimicrobial and chemotherapy resistance are escalating medical problem of paramount importance. Yet, research for novel antimicrobial and anticancer agents remains lagging behind. With their reported medical applications, DNA minor groove binders (MGBs) are worthy of exploration. In this study, the approach of structure-based drug design was implemented to generate 11 MGB compounds including a novel class of bioactive alkyne-linked MGBs. The NCI screening protocol was utilized to evaluate the antitumor activity of the target MGBs. Furthermore, a variety of bactericidal, cytopathogenicity, MIC90, and cytotoxicity assays were carried out using these MGBs against 6 medically relevant bacteria: Salmonella enterica, Escherichia coli, Serratia marcescens, Bacillus cereus, Streptococcus pneumoniae and Streptococcus pyogenes. Moreover, molecular docking, molecular dynamic simulations, DNA melting, and isothermal titration calorimetry (ITC) analyses were utilized to explore the binding mode and interactions between the most potent MGBs and the DNA duplex d(CGACTAGTCG)2. NCI results showed that alkyne-linked MGBs (26 & 28) displayed the most significant growth inhibition among the NCI-60 panel. In addition, compounds MGB3, MGB4, MGB28, and MGB32 showed significant bactericidal effects, inhibited B. cereus and S. enterica-mediated cytopathogenicity, and exhibited low cytotoxicity. MGB28 and MGB32 demonstrated significant inhibition of S. pyogenes, whereas MGB28 notably inhibited S. marcescens and all four minor groove binders significantly inhibited B. cereus. The ability of these compounds to bind with DNA and distort its groove dimensions provides the molecular basis for the allosteric perturbation of proteins-DNA interactions by MGBs. This study shed light on the mechanism of action of MGBs and revealed the important structural features for their antitumor and antibacterial activities, which are important to guide future development of MGB derivatives as novel antibacterial and anticancer agents.


Asunto(s)
Antibacterianos , Antineoplásicos , ADN , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Humanos , Relación Estructura-Actividad , ADN/química , ADN/metabolismo , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular
5.
Sci Rep ; 14(1): 8801, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627455

RESUMEN

This paper presents a study investigating the performance of functionally graded material (FGM) annular fins in heat transfer applications. An annular fin is a circular or annular structure used to improve heat transfer in various systems such as heat exchangers, electronic cooling systems, and power generation equipment. The main objective of this study is to analyze the efficiency of the ring fin in terms of heat transfer and temperature distribution. The fin surfaces are exposed to convection and radiation to dissipate heat. A supervised machine learning method was used to study the heat transfer characteristics and temperature distribution in the annular fin. In particular, a feedback architecture with the BFGS Quasi-Newton training algorithm (trainbfg) was used to analyze the solutions of the mathematical model governing the problem. This approach allows an in-depth study of the performance of fins, taking into account various physical parameters that affect its performance. To ensure the accuracy of the obtained solutions, a comparative analysis was performed using guided machine learning. The results were compared with those obtained by conventional methods such as the homotopy perturbation method, the finite difference method, and the Runge-Kutta method. In addition, a thorough statistical analysis was performed to confirm the reliability of the solutions. The results of this study provide valuable information on the behavior and performance of annular fins made from functionally graded materials. These findings contribute to the design and optimization of heat transfer systems, enabling better heat management and efficient use of available space.

6.
Heliyon ; 10(8): e29491, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38681612

RESUMEN

Background: White pitaya, a popular tropical fruit, is known for its high nutritional value. It is commercially cultivated worldwide for its potential use in the food and pharmaceutical industries. This study aims to assess the nutritional and phytochemical contents and biological potential of the South Chinese White Pitaya (SCWP) peel, flesh, and seed extracts. Methods: Extract fractions with increasing polarity (ethyl acetate < acetone < ethanol < methanol < aqueous) were prepared. Antibacterial potential was tested against multidrug-resistant (MDR) bacteria, and antioxidant activity was determined using, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assays, and cytotoxic activity against human keratinocyte cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Pharmacological screening and molecular docking simulations were conducted to identify potential antibacterial compounds with druggable characteristics. Molecular dynamics simulation (MDS) was employed to validate the binding stability of the promising ligand-protein complexes. Results: All parts of the fruit exhibited a substantial amount of crucial nutrients (minerals, sugars, proteins, vitamins, and fatty acids). The ethanol (ET) and acetone (AC) fractions of all samples demonstrated notable inhibitory effects against tested MDR bacteria, with MIC50 ranges of 74-925 µg/mL. Both ET and AC fractions also displayed remarkable antioxidant activity, with MIC50 ranges of 3-39 µg/mL. Cytotoxicity assays on HaCaT cells revealed no adverse effects from the crude extract fractions. LC-MS/MS analyses identified a diverse array of compounds, known and unknown, with antibacterial and antioxidant activities. Molecular docking simulations and pharmacological property screening highlighted two active compounds, baicalein (BCN) and lenticin (LTN), showing strong binding affinity with selected target proteins and adhering to pharmacological parameters. MDS indicated a stable interaction between the ligands (BCN and LTN) and the receptor proteins over a 100-ns simulation period. Conclusion: Our study provides essential information on the nutritional profile and pharmacological potential of the peel, flesh, and seeds of SCWP. Furthermore, our findings contribute to the identification of novel antioxidants and antibacterial agents that could be capable of overcoming the resistance barrier posed by MDR bacteria.

7.
Front Med (Lausanne) ; 11: 1389329, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590313

RESUMEN

Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as liver fibrosis. Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic liver injury. Exploring potential therapeutic targets and understanding the molecular mechanisms involved in liver fibrosis are essential for the development of effective interventions. The goal of this comprehensive review is to explain how the PI3K/AKT signaling pathway contributes to the reduction of liver fibrosis. The potential of this pathway as a therapeutic target is investigated through a summary of results from in vivo and in vitro studies. Studies focusing on PI3K/AKT activation have shown a significant decrease in fibrosis markers and a significant improvement in liver function. The review emphasizes how this pathway may prevent ECM synthesis and hepatic stellate cell (HSC) activation, ultimately reducing the fibrotic response. The specific mechanisms and downstream effectors of the PI3K/AKT pathway in liver fibrosis constitute a rapidly developing field of study. In conclusion, the PI3K/AKT signaling pathway plays a significant role in attenuating liver fibrosis. Its complex role in regulating HSC activation and ECM production, demonstrated both in vitro and in vivo, underscores its potential as a effective therapeutic approach for managing liver fibrosis and slowing disease progression. A comprehensive review of this field provides valuable insights into its future developments and implications for clinical applications.

8.
Int J Pharm X ; 7: 100238, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38511068

RESUMEN

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

9.
Int J Biol Macromol ; 263(Pt 1): 130694, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38458284

RESUMEN

Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.


Asunto(s)
Melanoma , Nanopartículas del Metal , Neoplasias Cutáneas , Óxido de Zinc , Animales , Humanos , Óxido de Zinc/farmacología , Óxido de Zinc/química , Espectroscopía Infrarroja por Transformada de Fourier , Melanoma/tratamiento farmacológico , Albúmina Sérica Bovina/química , Neoplasias Cutáneas/tratamiento farmacológico , Estrés Oxidativo , Antibacterianos/farmacología , Nanopartículas del Metal/química , Extractos Vegetales/química
10.
Int Ophthalmol ; 44(1): 140, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491335

RESUMEN

Keratitis is corneal inflammatory disease which may be caused by several reason such as an injury, allergy, as well as a microbial infection. Besides these, overexposure to ultraviolet light and unhygienic practice of contact lenses are also associated with keratitis. Based on the cause of keratitis, different lines of treatments are recommended. Photodynamic therapy is a promising approach that utilizes light activated compounds to instigate either killing or healing mechanism to treat various diseases including both communicable and non-communicable diseases. This review focuses on clinically-important patent applications and the recent literature for the use of photodynamic therapy against keratitis.


Asunto(s)
Lentes de Contacto , Enfermedades de la Córnea , Queratitis , Fotoquimioterapia , Humanos , Queratitis/tratamiento farmacológico , Queratitis/etiología , Córnea , Enfermedades de la Córnea/complicaciones , Fotoquimioterapia/efectos adversos
11.
Arch Microbiol ; 206(4): 134, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38433145

RESUMEN

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.


Asunto(s)
Acanthamoeba castellanii , Micelas , Humanos , Itraconazol/farmacología , Alquinos , Polímeros
12.
Plant Foods Hum Nutr ; 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363439

RESUMEN

Red dragon fruit is gaining popularity globally due to its nutritional value and bioactive components. The study aimed to assess the phytochemical, nutritional composition, antioxidant, antibacterial, and cytotoxic properties of extracts from the South Chinese red dragon fruit peel, flesh, and seeds. Extract fractions with increasing polarity (ethyl acetate

13.
Phys Rev Lett ; 132(5): 053801, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38364161

RESUMEN

Bloch oscillations refer to the periodic oscillation of a wave packet in a lattice under a constant force. Typically, the oscillation has a fundamental period that corresponds to the wave packet traversing the first Brillouin zone once. Here, we demonstrate, both theoretically and experimentally, the optical Bloch oscillations where the wave packet must traverse the first Brillouin zone twice to complete a full cycle, resulting in a period of oscillation that is 2 times longer than that of usual Bloch oscillations. The unusual Bloch oscillations arise due to the band crossing of valley-Hall topological edge states at the Brillouin boundary for zigzag domain walls between two staggered honeycomb lattices with inverted on-site energy detuning, which are protected by the glide-reflection symmetry of the underlying structures. Our work sheds light on the direct detection of band crossings resulting from intrinsic symmetries that extend beyond the fundamental translational symmetry in topological systems.

14.
Parasitol Res ; 123(2): 117, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294565

RESUMEN

The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.


Asunto(s)
Acanthamoeba castellanii , Amebiasis , Amebicidas , Quistes , Humanos , Lactasa , Galactosa , Soluciones para Lentes de Contacto , Genotipo , Glucosa , Diferenciación Celular
15.
Heliyon ; 10(1): e23258, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38205285

RESUMEN

A rare but lethal central nervous system disease known as granulomatous amoebic encephalitis (GAE) and potentially blinding Acanthamoeba keratitis are diseases caused by free-living Acanthamoeba. Currently, no therapeutic agent can completely eradicate or prevent GAE. Synthetic compounds are a likely source of bioactive compounds for developing new drugs. This study synthesized seventeen 1,4-benzothiazine derivatives (I -XVII) by a base-catalyzed one-pot reaction of 2-amino thiophenol with substituted bromo acetophenones. Different spectroscopic techniques, such as EI-MS, 1H-, and 13C NMR (only for the new compounds), were used for the structural characterization and conformation of compounds. These compounds were assessed for the first time against Acanthamoeba castellanii. All compounds showed anti-amoebic potential in vitro against A. castellanii, reducing its ability to encyst and excyst at 100 µM. Compounds IX, X, and XVI showed the most potent activities among all derivatives and significantly reduced the viability to 5.3 × 104 (p < 0.0003), 2 × 105 (p < 0.006), and 2.4 × 105 (p < 0.002) cells/mL, respectively. The cytotoxicity profile revealed that these molecules showed lower to moderate cytotoxicity, i.e., 36 %, 2 %, and 21 %, respectively, against human keratinocytes in vitro. These results indicate that 1,4-benzothiazines showed potent in vitro activity against trophozoites and cysts of A. castellanii. Hence, these 1,4-benzothiazine derivatives should be considered to develop new potential therapeutic agents against Acanthamoeba infections.

16.
Heliyon ; 10(1): e23592, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38187258

RESUMEN

Microgravity, in space travel and prolonged bed rest conditions, induces cardiovascular deconditioning along with skeletal muscle mass loss and weakness. The findings of microgravity research may also aid in the understanding and treatment of human health conditions on Earth such as muscle atrophy, and cardiovascular diseases. Due to the paucity of biomarkers and the unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these environments, there are insufficient diagnostic and preventative measures. In this study, we employed hindlimb unloading (HU) mouse model, which mimics astronauts in space and bedridden patients, to first evaluate cardiovascular and skeletal muscle function, followed by proteomics and metabolomics LC-MS/MS-based analysis using serum samples. Three weeks of unloading caused changes in the function of the cardiovascular system in c57/Bl6 mice, as seen by a decrease in mean arterial pressure and heart weight. Unloading for three weeks also changed skeletal muscle function, causing a loss in grip strength in HU mice and atrophy of skeletal muscle indicated by a reduction in muscle mass. These modifications were partially reversed by a two-week recovery period of reloading condition, emphasizing the significance of the recovery process. Proteomics analysis revealed 12 dysregulated proteins among the groups, such as phospholipid transfer protein, Carbonic anhydrase 3, Parvalbumin alpha, Major urinary protein 20 (Mup20), Thrombospondin-1, and Apolipoprotein C-IV. On the other hand, metabolomics analysis showed altered metabolites among the groups such as inosine, hypoxanthine, xanthosine, sphinganine, l-valine, 3,4-Dihydroxyphenylglycol, and l-Glutamic acid. The joint data analysis revealed that HU conditions mainly impacted pathways such as ABC transporters, complement and coagulation cascades, nitrogen metabolism, and purine metabolism. Overall, our results indicate that microgravity environment induces significant alterations in the function, proteins, and metabolites of these mice. These observations suggest the potential utilization of these proteins and metabolites as novel biomarkers for assessing and mitigating cardiovascular and skeletal muscle deconditioning associated with such conditions.

17.
SAGE Open Med Case Rep ; 12: 2050313X231222222, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38187812

RESUMEN

Actinomycosis is a rare, chronic, and suppurative disease caused by Actinomyces species, which are filamentous, obligate, Gram-positive bacteria. This report presents a case of anterior abdominal actinomycosis in a 40-year-old female with a history of intrauterine contraceptive device placement. The patient presented with severe abdominal pain, an abdominal mass, low-grade fever, and weight loss. Imaging studies revealed thickening of the left rectus abdominis muscle and pericolic fat stranding. An exploratory laparotomy confirmed dense adhesions from the transverse colon and omentum to the abdominal wall with a purulent discharge. Resection of the affected colon segment and primary anastomosis were performed. Histopathological examination revealed characteristic colonies of Actinomyces within abscesses, confirming the diagnosis of actinomycosis. The patient received appropriate antibiotic therapy and showed improvement. This case highlights the rare occurrence of abdominal wall actinomycosis associated with an intrauterine contraceptive device and emphasizes the importance of considering actinomycosis in the differential diagnosis of abdominal pathologies. Thus, medical history related to intrauterine contraceptive device use should be regarded as in differentials if a patient presents vague abdominal mass and pain, and small details in history should be emphasized and looked upon so that a timely decision can be made for the betterment of the patient.

18.
Life Sci Space Res (Amst) ; 40: 62-71, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38245349

RESUMEN

During space travel, the gut microbiota is changed which can lead to health-related issues. Previously, we utilized the hind-limb unloaded (HU) mouse, which is an established ground-based in-vivo model of microgravity and observed altered gut microbiota. In this study, we evaluated the beneficial effects of novel bacterial conditioned media in HU mice to understand if they can offset the effects of unloading in the HU mouse model. We aimed to explore the influence of bacterial conditioned media on diversity and quantity of intestinal microbes in HU mice, and investigated the microarchitecture of mice retinas and kidneys to evaluate the potential systemic effects of bacterial conditioned media in HU mice. Four-month-old, male C57/Bl6 mice were separated into groups: including the ground-based control group, the HU group mice fed with vehicle as placebo (HU-placebo mice), and the HU group fed with bacterial conditioned media (HU-CP mice) and kept under controlled environmental conditions for three weeks. Next, mice were sacrificed; gut dissections were conducted, and metagenomic analysis of bacterial species was performed via DNA extraction and 16S rRNA analysis. The results revealed an HU-induced reduction in intestinal microbial diversity, and an increase in pathogenic bacteria dominated by Firmicutes (45%). In contrast, supplementation with bacterial conditioned media for three weeks led to a significant increase in gut microbial diversity with noticeable changes in the OTUs abundance in the HU mice. Additionally, HU-induced muscle weakness and structural abnormalities in the retina and kidney were partially prevented with bacterial conditioned media. Moreover, a greater diversity of several bacteria in the HU-CP was observed including, Bacteriodota, Firmicutes, Proteobacteria, Actionobacteriota, Verrucomicorbiota, Cyanobacteria, Gemmatimonadota, Acidobacteriota, Chloroflexi, Myxococcota, and others. Prospective research involving molecular mechanistic studies are needed to comprehend the systemic effects of bacterial metabolites conditioned media on experimental animal models under chronic stress.


Asunto(s)
Cianobacterias , Microbioma Gastrointestinal , Ratones , Masculino , Animales , ARN Ribosómico 16S/genética , Medios de Cultivo Condicionados , Estudios Prospectivos , Microbioma Gastrointestinal/genética
19.
Life Sci Space Res (Amst) ; 40: 89-96, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38245353

RESUMEN

In view of the critical role the gut microbiome plays in human health, it has become clear that astronauts' gut microbiota composition changes after spending time in space. Astronauts are exposed to several risks in space, including a protracted period of microgravity, radiation, and mechanical unloading of the body. Several deleterious effects of such an environment are reported, including orthostatic intolerance, cardiovascular endothelial dysfunction, cellular and molecular changes, and changes in the composition of the gut microbiome. Herein, the correlation between the gut microbiome and cardiovascular disease in a microgravity environment is evaluated. Additionally, the relationship between orthostatic hypotension, cardiac shrinkage and arrhythmias during spaceflight, and cellular alterations during spaceflight is reviewed. Given its impact on human health in general, modifying the gut microbiota may significantly promote astronaut health and performance. This is merited, given the prospect of augmented human activities in future space missions.


Asunto(s)
Microbioma Gastrointestinal , Vuelo Espacial , Ingravidez , Humanos , Ingravidez/efectos adversos , Astronautas , Corazón
20.
Colloids Surf B Biointerfaces ; 234: 113762, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38244483

RESUMEN

Gastric ulcers are worrying, and their worsening conditions may result in bleeding in the internal lining of the stomach. The problem is annoying, and both patients and professionals are still not satisfied with the available treatment options. Hesperidin, a flavonoid molecule with potent anti-inflammatory and antioxidant effects, can work like witchcraft to repair gastric ulcers and preserve the stomach lining. Here, we employed a strategy that involved covering the surface of the nano-lipid carriers (NLCs) with sericin before encasing the hesperidin within (Se-He-NLC). Sericin, a biodegradable polymer increases the muco-adhesion with stomach lining and deployment of hesperidin in controlled manner. Se-He-NLCs were physico-chemically characterized for drug loading, encapsulation, particle size, morphology, drug release, chemical stability, and chemical bonding. The nanocarriers showed first order drug release in a controlled manner. Se-He-NLCs showed better in vitro permeation and ex vivo mucoadhesion, thereby by promoting the in vivo bioavailability. Se-He-NLCs also promoted the reduced glutathione (GSH) and glutathione-S-transferase (GST) levels by 2.24- and 1.61-folds, respectively in the stomach lining, and also the regulation of superoxide dismutase (SOD) and catalase (CAT) activities parallel to the control group. In addition, tissues lipid hydroperoxides (LOOH) and myeloperoxidase (MPO) activity were reduced significantly with Se-He-NLCs administration. Se-He-NLC therapy of stomach ulcers in vivo demonstrated better binding ratio and ulcer healing potential. This approach reveals huge capacity for delivering therapies to treat gastric ulcers based on the clinical significance of sericin coated hesperidin nanocarriers in gastric ulcer treatment.


Asunto(s)
Hesperidina , Nanopartículas , Sericinas , Úlcera Gástrica , Humanos , Ratas , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Hesperidina/farmacología , Ratas Wistar , Antioxidantes/metabolismo , Superóxido Dismutasa/metabolismo
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