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1.
Biomaterials ; 312: 122744, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39106820

ABSTRACT

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.


Subject(s)
Carbon Monoxide , Light , Postoperative Cognitive Complications , Animals , Postoperative Cognitive Complications/etiology , Postoperative Cognitive Complications/metabolism , Male , Mice , Mice, Inbred C57BL , Nanoparticles/chemistry , Micelles , Red Light
2.
Biomaterials ; 312: 122749, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39121725

ABSTRACT

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.


Subject(s)
Alzheimer Disease , Apoptosis , Blood-Brain Barrier , Methylene Blue , Nanomedicine , Neuroinflammatory Diseases , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Apoptosis/drug effects , PC12 Cells , Neuroinflammatory Diseases/drug therapy , Rats , Mice , Nanomedicine/methods , Methylene Blue/pharmacology , Methylene Blue/therapeutic use , Male , Reactive Oxygen Species/metabolism , Mice, Inbred C57BL
3.
Methods Mol Biol ; 2847: 33-43, 2025.
Article in English | MEDLINE | ID: mdl-39312135

ABSTRACT

In silico design of artificial riboswitches is a challenging and intriguing task. Since experimental approaches such as in vitro selection are time-consuming processes, computational tools that guide riboswitch design are desirable to accelerate the design process. In this chapter, we describe the usage of the MODENA web server to design ON riboswitches on the basis of a multi-objective genetic algorithm and RNA secondary structure prediction.


Subject(s)
Algorithms , Computational Biology , Nucleic Acid Conformation , Riboswitch , Software , Computational Biology/methods
4.
Immun Ageing ; 21(1): 65, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350153

ABSTRACT

BACKGROUND: The intestinal barrier encompasses physical and immunological components that act to compartmentalize luminal contents, such as bacteria and endotoxins, from the host. It has been proposed that an age-related decline of intestinal barrier function may allow for the passage of luminal contents into the bloodstream, triggering a low-grade systemic inflammation termed inflamm-aging. Although there is mounting evidence to support this hypothesis in model species, it is unclear if this phenomenon occurs in humans. In addition, despite being well-established that biological sex impacts aging physiology, its influence on intestinal barrier function and inflamm-aging has not been explored. RESULTS: In this study, we observed sex differences in markers of intestinal barrier integrity, where females had increased epithelial permeability throughout life as compared to males. With age, females had an age-associated increase in circulating bacterial products and metabolites such as LPS and kynurenine, suggesting reduced barrier function. Females also had age-associated increases in established markers of inflamm-aging, including peripheral blood monocytes as well as TNF and CRP. To determine if impaired barrier function was driving inflamm-aging, we performed a mediation analysis. The results show that the loss of intestinal barrier integrity was not the mediator of inflamm-aging in humans. Instead, persistent, low-grade inflammation with age preceded the increase in circulating bacterial products, which we confirmed using animal models. We found, as in humans, that sex modified age-associated increases in circulating monocytes in mice, and that inflammation mediates the loss of intestinal barrier function. CONCLUSION: Taken together, our results suggest that higher basal intestinal permeability in combination with age-associated inflammation, increases circulating LPS in females. Thus, targeting barrier permeability in females may slow the progression of inflamm-aging, but is unlikely to prevent it.

5.
Curr Drug Saf ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39350403

ABSTRACT

The blood-brain barrier (BBB) is based on the unique pattern of the microvasculature of the central nervous system (CNS), which controls the transport of molecules between the CNS and the blood. The blood-brain barrier is mainly composed of endothelial cells, pericytes, and basement membrane, as well as the astrocytes and immune cells as perivascular macrophages and microglial cells. The dysfunction of this barrier can cause serious neuronal disorders due to the transport of hazardous molecules and immune cells to the CNS. Mitochondria plays a major role in cellular homeostasis in terms of health and disease. This review evaluated the published data about the effect of the drugs on the cells of BBB. Only seven articles were found that considered the effect of drugs on the barrier endothelial cells and mitochondria via different assays. Further studies are recommended to evaluate the impact of used medications on BBB cell bioenergetics. Also, the effect of the newly studied pharmaceutical agents on the BBB bioenergetics should be included within their safety profile studies.

6.
Adv Mater ; : e2410355, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350446

ABSTRACT

Balancing optical modulation and response time is crucial for achieving high coloration efficiency in electrochromic materials. Here, internal electric fields are introduced to titanium dioxide nanosheets by constructing abundant amorphous-crystalline interfaces, ensuring large optical modulation while reducing response time and therefore improving coloration efficiency. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) reveals the presence of numerous amorphous-crystalline phase boundaries in titanium dioxide nanosheets. Kelvin probe force microscopy (KPFM) exhibits an intense surface potential distribution, demonstrating the presence of internal electric fields. Density functional theory (DFT) calculations confirm that the amorphous-crystalline heterointerfaces can generate internal electric fields and reduce diffusion barriers of lithium ions. As a result, the amorphous-crystalline titanium dioxide nanosheets exhibit better coloration efficiency (35.1 cm2 C-1) than pure amorphous and crystalline titanium dioxide nanosheets.

7.
Adv Mater ; : e2411015, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350462

ABSTRACT

The potential of hybrid perovskite/organic solar cells (HSCs) is increasingly recognized owing to their advantageous characteristics, including straightforward fabrication, broad-spectrum photon absorption, and minimal open-circuit voltage (VOC) loss. Nonetheless, a key bottleneck for efficiency improvement is the energy level mismatch at the perovskite/bulk-heterojunction (BHJ) interface, leading to charge accumulation. In this study, it is demonstrated that introducing a uniform sub-nanometer dipole layer formed of B3PyMPM onto the perovskite surface effectively reduces the 0.24 eV energy band offset between the perovskite and the donor of BHJ. This strategic modification suppresses the charge recombination loss, resulting in a noticeable 30 mV increase in the VOC and a balanced carrier transport, accompanied by a 5.0% increase in the fill factor. Consequently, HSCs that achieve power conversion efficiency of 24.0% is developed, a new record for Pb-based HSCs with a remarkable increase in the short-circuit current of 4.9 mA cm-2, attributed to enhanced near-infrared photon harvesting.

8.
Yale J Biol Med ; 97(3): 349-363, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39351324

ABSTRACT

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD.


Subject(s)
Blood-Brain Barrier , Depressive Disorder, Major , Fatty Acids, Omega-3 , Neuroinflammatory Diseases , Humans , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/metabolism , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/drug therapy , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/drug therapy , Neuroprotection , Animals , Inflammation/metabolism , Inflammation/drug therapy
9.
Front Endocrinol (Lausanne) ; 15: 1430334, 2024.
Article in English | MEDLINE | ID: mdl-39351527

ABSTRACT

Glucocorticoids (GCs) are steroid hormones fundamental to the body's normal physiological functions and are pivotal in fetal growth and development. During gestation, the mother's cortisol concentration (active GCs) escalates to accommodate the requirements of fetal organ development and maturation. A natural placental GCs barrier, primarily facilitated by 11ß hydroxysteroid dehydrogenase 2, exists between the mother and fetus. This enzyme transforms biologically active cortisol into biologically inactive corticosterone, thereby mitigating fetal GCs exposure. However, during pregnancy, the mother may be vulnerable to adverse factor exposures such as stress, hypoxia, caffeine, and synthetic GCs use. In these instances, maternal serum GCs levels may surge beyond the protective capacity of the placental GCs barrier. Moreover, these adverse factors could directly compromise the placental GCs barrier, resulting in excessive fetal exposure to GCs. It is well-documented that prenatal GCs exposure can detrimentally impact the offspring's cardiovascular system, particularly in relation to blood pressure, vascular function, and heart function. In this review, we succinctly delineate the alterations in GCs levels during pregnancy and the potential mechanisms driving these changes, and also analyze the possible causes of prenatal GCs exposure. Furthermore, we summarize the current advancements in understanding the adverse effects and mechanisms of prenatal GCs exposure on the offspring's cardiovascular system.


Subject(s)
Glucocorticoids , Prenatal Exposure Delayed Effects , Pregnancy , Humans , Female , Glucocorticoids/adverse effects , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Animals , Cardiovascular System/drug effects , Cardiovascular System/metabolism , Cardiovascular Diseases/chemically induced , Fetal Development/drug effects , Placenta/metabolism , Placenta/drug effects
10.
Nano Lett ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39351960

ABSTRACT

There is an increasing demand for p-type semiconductors with scalable growth, excellent device performance, and back-end-of-line (BEOL) compatibility. Recently, tellurium (Te) has emerged as a promising candidate due to its appealing electrical properties and potential low-temperature production. So far, nearly all of the scalable production and integration of Te with complementary metal oxide semiconductor (CMOS) technology have been based on physical vapor deposition. Here we demonstrate wafer-scale atomic layer-deposited (ALD) TeOx/Te heterostructure thin-film transistors with high uniformity and integration compatibility. The wafer-scale uniformity of the film is evidenced by spatial Raman mappings and statistical electrical analysis. Furthermore, surface accumulation-induced good ohmic contact has been observed and explained by the unique band alignment of the charge neutrality level inside the Te valence band. These results demonstrate ALD TeOx/Te as a promising p-type semiconductor for monolithic three-dimensional integration in BEOL CMOS applications incorporated with well-established n-type ALD oxide semiconductors.

11.
Plant Cell Rep ; 43(10): 248, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39354144

ABSTRACT

KEY MESSAGE: Embryo abortion at the heart-shaped stage is the main reason for the failure of interspecific hybridization of hydrangea, and salicylic acid plays a key role during embryo abortion. Difficulties in obtaining seeds from interspecific hybridization between Hydrangea macrophylla and H. arborescens had severely restricted the process of breeding new hydrangea varieties. To clarify the cause of reproductive barriers, an interspecific hybridization was made between H. macrophylla 'Endless Summer' (female parent) and H. arborescens 'Annabelle' (male parent). The results showed that both parents' floral organs developed normally, 'Annabelle' had high pollen viability (84.83% at 8 h after incubation), and the pollen tube could enter into the ovule of 'Endless Summer' at 72 h after pollination. Therefore, the pre-fertilization barrier was not the main reason for the failure of interspecific hybridization. However, observation of the embryo development by paraffin sections showed that the embryo was aborted at the heart-shaped stage. In addition, salicylic acid (SA) content was significantly higher (fourfold, P < 0.01) at 21 days after pollination (DAP) as compared to that of 17 DAP, which means SA may be closely correlated with embryo development. A total of 957 metabolites were detected, among which 78 were significantly different. During the embryo abortion, phenylpropanoids and polyketides were significantly down-regulated, while organic oxygen compounds were significantly up-regulated. Further analysis indicated that the metabolic pathway was enriched in the shikimic acid biosynthesis pathway, which suggests that more SA was synthesized. Taken together, it can be reasonably speculated that SA plays a key role leading to embryo abortion underlying the interspecific hybridization between Hydrangea macrophylla and H. arborescens. The result is helpful to direct the breeding of hydrangea through distant hybridization.


Subject(s)
Hybridization, Genetic , Hydrangea , Salicylic Acid , Seeds , Salicylic Acid/metabolism , Seeds/genetics , Seeds/metabolism , Seeds/growth & development , Hydrangea/genetics , Hydrangea/metabolism , Metabolomics/methods , Pollination , Pollen/genetics , Pollen/metabolism , Pollen/growth & development , Flowers/genetics , Flowers/metabolism , Flowers/growth & development , Gene Expression Regulation, Plant
12.
Article in English | MEDLINE | ID: mdl-39354215

ABSTRACT

The purpose of this study was to investigate the improvement of the intestinal barrier and gut microbiota in mice with antibiotic-associated diarrhea (AAD) using Lactiplantibacillus plantarum ELF051 combined with Astragalus polysaccharides. The amoxicillin, clindamycin, and streptomycin triple-mixed antibiotic-induced AAD models were administered with L. plantarum ELF051 or Astragalus polysaccharides or L. plantarum ELF051 + Astragalus polysaccharides for 14 days. Our findings revealed that the combination of L. plantarum ELF051 and Astragalus polysaccharides elevated the number of goblet cells and enhanced the proportion of mucous within the colon tissue. Furthermore, the expression of sIgA and IgG were upregulated, while the levels of IL-17A, IL-4, DAO, D-LA, LPS, and TGF-ß1 were downregulated. L. plantarum ELF051 combined with Astragalus polysaccharides elevated the expression of tight junction (TJ) proteins, facilitating intestinal mucosal repair via Smad signaling nodes. Furthermore, their combination effectively increased the relative abundance of lactic acid bacteria (LAB) and Allobaculum, and decreased the relative abundance of Bacteroides and Blautia. Spearman rank correlation analysis demonstrated that LAB were closely related to permeability factors, immune factors, and indicators of intestinal barrier function. In summary, the effect of combining L. plantarum ELF051 and Astragalus polysaccharides on AAD mice was achieved by enhancing intestinal barrier function and regulating the composition of the gut microbiota.

13.
Article in English | MEDLINE | ID: mdl-39352537

ABSTRACT

5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella, which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter, which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.

14.
Int Immunopharmacol ; 142(Pt A): 113023, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39217886

ABSTRACT

Corneal neovascularization (CoNV) is the second leading cause of visual impairment worldwide, and current drugs have certain limitations. Inflammatory response is the core pathological process of CoNV. Neutrophil extracellular traps (NETs) are generated after neutrophil activation, which promotes neovascularization. Prior studies demonstrated that bone morphogenetic protein 4 (BMP4) could significantly reduce inflammation and CoNV formation, its exact molecular mechanism remains unclear. Therefore, we stimulated human peripheral blood neutrophils with phorbol myristate acetate (PMA) or deoxyribonuclease I (DNase I) to induce or inhibit NETs formation. By using corneal sutures and subconjunctival injections of NETs or DNase I, rat CoNV models were established. Compared with the suture group, NETs formation and inflammatory cell infiltration in the corneal stroma were significantly increased, corneal edema was aggravated, and the length, area and diameter of CoNV were significantly enhanced in the NETs group. Furthermore, by curetting the corneal epithelial apical junctional complexes (AJCs), a crucial component in preserving the function of the corneal epithelial barrier, we discovered that the damage of AJCs had a significant role in inducing CoNV formation. NETs could induce CoNV formation by injuring corneal epithelial AJCs. Finally, by comparing the aforementioned indicators after the intervention of BMP4, BMP4 inhibitor Noggin and NADPH oxidase (NOX) inhibitor, we finally demonstrated that BMP4 could inhibit NETs-induced inflammation and corneal epithelial AJC injury, repair corneal epithelial barrier function and eventually inhibit CoNV formation by blocking NOX-2-dependent NETs formation.

15.
J Dairy Sci ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39218063

ABSTRACT

This study evaluated the impact of short-term feed restriction in lactating dairy cows on regional permeability of the gastrointestinal tract (GIT), and the recovery of DMI, ruminal pH, and milk yield. In addition, sampling methods for a novel dual marker technique to characterize total GIT and post ruminal permeability were validated. Six ruminally cannulated lactating Holstein cows were blocked by parity (3 primiparous, 3 multiparous; 189 DIM ± 25.2) and enrolled in a crossover design. Experimental periods included a 5-d baseline phase (BASE), 5-d challenge phase (CHAL), and 2 weeks of recovery (REC1 and REC2). During CHAL cows received either 100% ad libitum feed intake (AL) or 40% of ad libitum feed intake (FR). To assess, total-tract and post-ruminal permeability, equimolar doses of Cr-EDTA and Co-EDTA were infused on d 3 of CHAL into the rumen and abomasum (0.369 mmol/kg BW). Following infusions, total urine and feces were collected every 8 h over 96 h, and blood samples were collected at h 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, and 64. The plasma area under the curve (AUC) for Cr and Co were calculated. By design, DMI for FR was reduced by 60% during CHAL and remained 19% lower than AL during REC1 but was not different from AL in REC2. Mean ruminal pH for FR was greatest during CHAL and the least during REC1, with no differences detected between AL and FR in REC2. The duration that pH was < 5.8 was the least for FR during CHAL and greatest during REC1 which were different from AL and were no longer different between treatments in REC2. Milk yield was the least for FR during CHAL and REC1 and no longer different from AL in REC2. Feed restriction reduced milk fat, protein, and lactose yields by 26, 31% and 31%, respectively. Plasma Cr AUC was 34% greater and Co AUC tended to be 35% greater for FR than AL on d 3 of CHAL. Urinary Cr recovery after 48-h was not affected by treatment; however, urinary Co recovery was 36% greater for FR than AL. Positive correlations between plasma AUC and urinary recovery for Cr and Co were detected. It was determined that blood samples collected at h 2, 8, 20, 40, and 48 could predict the total plasma Cr and Co AUC within 1.9% and 6.2%, respectively. In summary, short-term FR in lactating dairy cows increases permeability of the total GIT and may increase permeability of the post-ruminal regions with more than 60% of the permeability occurring post-ruminally. After FR, cows experienced low ruminal pH and a sustained reduction in milk yield. When utilizing Cr- and Co-EDTA to evaluate regional GIT permeability, plasma AUC can be used as an alternate to urinary Cr and Co excretion. In addition, blood samples collected at h 2, 8, 20, 40, and 48 result in adequate prediction accuracy, at least when comparing GIT permeability for lactating dairy cows exposed to AL and FR.

16.
Carbohydr Polym ; 344: 122517, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39218542

ABSTRACT

Grifola frondosa polysaccharide (GFP) is a consumable fungus recognized for its potential health advantages. The present study aimed to investigate the development and potential etiologies of ulcerative colitis (UC) utilizing oxazolone (OXZ) as an inducer in mice, along with assessing the therapeutic effects of GFP at varying doses in UC mice, with sulfasalazine (SASP) serving as the positive control. The obtained results indicated that OXZ intervention in mice induced numerous physical manifestations of UC, including increased disease activity index (DAI), decreased goblet cell division, enhanced fibrosis, reduced expression of Claudin1 and Zona encludens protein1 (ZO-1), decreased proliferative activity of colonic mucosal epithelial cells, disturbed oxidation balance, and alterations in intestinal flora. Nonetheless, GFP intervention significantly ameliorated or even resolved these abnormal indicators to a considerable extent. Consequently, this study suggests that GFP might serve as a prebiotic to regulate intestinal flora, mitigate enterotoxin production, restore oxidative balance, thereby reducing the generation of inflammatory mediators, restoring the intestinal barrier, and ultimately improving OXZ-induced UC in mice. GFP demonstrates promising potential as a candidate drug for colitis treatment and as a dietary supplement for alleviating intestinal inflammatory issues.


Subject(s)
Colitis, Ulcerative , Grifola , Oxazolone , Animals , Oxazolone/toxicity , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Mice , Grifola/chemistry , Male , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Colon/drug effects , Colon/pathology , Colon/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Gastrointestinal Microbiome/drug effects , Sulfasalazine/pharmacology
17.
J Inflamm Res ; 17: 5711-5721, 2024.
Article in English | MEDLINE | ID: mdl-39219814

ABSTRACT

The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.

18.
World J Gastrointest Surg ; 16(8): 2484-2493, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39220065

ABSTRACT

BACKGROUND: Gastric cancer remains a leading cause of cancer-related mortality globally. Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery. AIM: To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer, focusing on its potential to reduce trauma, accelerate recovery, and achieve comparable oncological outcomes. METHODS: This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December 2023. The patients were divided into two groups: Minimally invasive surgery group (n = 102), who underwent laparoscopic gastrectomy, and open surgery group (n = 101), who underwent traditional open gastrectomy. We compared surgical indicators (surgical incision size, intraoperative blood loss, surgical duration, and number of lymph nodes dissected), recovery parameters (time to first flatus, time to start eating, time to ambulation, and length of hospital stay), immune function (levels of IgA, IgG, and IgM), intestinal barrier function (levels of D-lactic acid and diamine oxidase), and stress response (levels of C-reactive protein, interleukin-6, and procalcitonin). RESULTS: The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators, including smaller incisions, less blood loss, shorter surgery time, and more lymph nodes dissected (P < 0.05 for all). Recovery was also faster in the minimally invasive surgery group, with earlier return of bowel function, earlier initiation of diet, quicker mobilization, and shorter hospital stays (P < 0.05 for all). Furthermore, patients in the minimally invasive surgery group had better preserved immune function, superior intestinal barrier function, and a less pronounced stress response postoperatively (P < 0.05 for all). CONCLUSION: Laparoscopic minimally invasive surgery for gastric cancer not only provides superior surgical indicators and faster recovery but also offers advantages in preserving immune function, protecting intestinal barrier function, and mitigating the stress response compared to traditional open surgery. These findings support the broader adoption of laparoscopic techniques in the management of gastric cancer.

19.
Acta Pharm Sin B ; 14(8): 3432-3456, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39220871

ABSTRACT

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune system. However, the challenge of practical and precise targeting of malignant cells persists. To address this, engineered nanoparticles (NPs) have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions, owing to their small size, low immunogenicity, and ease of surface modification. This comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy, encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic effectiveness. Moreover, it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic modalities. Finally, the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy, which could shape the path for future advancements in this promising field.

20.
Heliyon ; 10(16): e35923, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39220989

ABSTRACT

This paper discusses service times based on vehicle class at barrier-operated toll booths. Service times were measured using four vehicle classifications: car (C), medium goods vehicle (MGV), trucks & bus (TB), and articulated truck (AT) with two payment options: electronic (ETC) and manual toll collection (MTC). Each toll booth has both payment systems and resulting in mixed toll booth utilization in terms of payment and vehicles. The collected data was utilized to estimate logistic regression, and non-parametric statistical tests were performed. Findings indicate, when vehicle size increases, so does service time for even ETC. Furthermore, logistic regression used to compute threshold service times shifting from ETC to MTC for C, MGV, TB, and AT, which were 5.92, 7.51, 10.00, and 12.80 s, respectively. The transition time for a vehicle switch from ETC to MTC based on the logistic curve is denoted by threshold service time. Below the threshold, ETC is more favorable option and affected by barrier and vehicle class. Overall, the results indicate that operators can benefit from more dynamic operational conditions facilitated by threshold service times, enabling adaptive and efficient toll booth operations. Additionally, these thresholds can serve as valuable measure of service quality for managing freeway exits.

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