Search Results (110)

Anastomotic leakage (AL) is a significant complication associated with elevated morbidity and mortality rates following colorectal surgery. This complication primarily arises due to impaired wound healing. Anastomotic and intestinal wound healing is generally divided into three phases: inflammation, proliferation, and remodeling. The physiological transition between these phases is primarily orchestrated by macrophages, which are key regulators of inflammation and tissue repair. They undergo sequential phenotypic changes from pro-inflammatory to anti-inflammatory states and are involved in the phagocytosis of bacteria or debris, but also attract fibroblasts for collagen production and deposition. Importantly, they can promote local perfusion by secreting pro-angiogenic and growth factors. Failure of this transition from pro- to anti-inflammatory properties is associated with AL, scarring, and fibrosis. Intestinal macrophages represent the largest pool of resident myeloid cells and are promising cellular targets for therapeutic interventions. In this narrative review, we focus on intestinal and anastomotic wound healing, highlight the dichotomous role of macrophages, and discuss potential therapeutic strategies. A detailed understanding of macrophage polarization, recruitment, and targeted modulation may enhance wound healing and prevent complications such as AL. Full article

Congenital heart disease (CHD) is the most common congenital anomaly worldwide and is associated with substantial infant morbidity and mortality. This narrative review synthesizes evidence linking CHD to alterations in the gut microbiome across neonatal, perioperative, and chronic stages and highlights a gut–heart–immune framework in which microbial imbalance, intestinal barrier dysfunction, and systemic inflammation may interact to influence clinical outcomes. Early infancy represents a potential window for microbiome and immune development, shaped by delivery mode and feeding, with many breastfed infants developing a Bifidobacterium-dominant community supported by human milk oligosaccharides. In CHD, abnormal splanchnic perfusion and hypoxemia, together with intensive care and perioperative exposures (fasting, delayed enteral feeding, antibiotics, acid suppression), may predispose to dysbiosis and impaired barrier function. Cardiac surgery with cardiopulmonary bypass can act as a “second hit,” with evidence of increased gut permeability, endotoxemia, inflammatory activation, and biomarker signals of enterocyte injury and tight-junction disruption. Clinically, these mechanisms align with gut-sensitive outcomes including necrotizing enterocolitis (especially in ductal-dependent lesions), feeding intolerance, and postoperative infection-risk phenotypes. Interventions show mixed evidence: human milk exposure appears protective for NEC risk, synbiotics demonstrated outcome benefits in a randomized trial of cyanotic CHD infants, while probiotics may modify dysbiosis without consistently preventing intestinal injury and require careful safety frameworks. Key research gaps include the need for longitudinal stage-based cohorts, integration of microbiome profiling with barrier injury and perfusion markers, and standardized safety monitoring in intervention trials. Full article

Background and Objectives: Intraoperative assessment of tissue perfusion remains a decisive but imperfect step in abdominal surgery. Surgeons still rely heavily on visual judgement when choosing bowel transection lines, constructing anastomoses, judging intestinal viability, or assessing graft reperfusion, even though these decisions are directly linked to anastomotic leak, conduit ischemia, postoperative liver dysfunction, and graft failure. Hyperspectral imaging (HSI) is an emerging contrast-free optical technology that generates quantitative maps of tissue oxygenation, hemoglobin distribution, water content, and near-infrared perfusion. The present review was designed to evaluate whether clinical intraoperative HSI has matured sufficiently to support a focused systematic review topic in abdominal surgery and to synthesize the currently available human evidence. Methods: A literature search was conducted up to 20 February 2026 using combinations of the terms “hyperspectral imaging”, “HSI”, “abdominal surgery”, “colorectal”, “hepatectomy”, “transplantation”, “pancreatoduodenectomy”, “esophagectomy”, “mesenteric ischemia”, and “intraoperative”. Eligible records were original human clinical studies evaluating intraoperative HSI in abdominal or transplant-related operations with perfusion, oxygenation, or tissue viability as a central endpoint. Review articles, animal studies, non-surgical diagnostic studies, and single-patient case reports were excluded. Data were synthesized narratively because of major heterogeneity in indications, designs, devices, timing of measurements, and reported outcomes. Results: Thirteen studies published between 2019 and 2024 met the eligibility criteria, representing 391 patients. The literature covered colorectal resection, acute mesenteric ischemia, esophageal reconstruction with gastric or colonic conduits, pancreatoduodenectomy, pancreas transplantation, major hepatectomy, liver transplantation, and minimally invasive system validation. Across colorectal studies, HSI frequently demonstrated discordance between visually selected and objectively perfused transection lines, with clinically relevant strategy changes in a substantial proportion of patients. In ischemic and transplant settings, HSI discriminated poorly perfused tissue, identified low near-infrared perfusion values associated with early allograft dysfunction, and quantified reperfusion patterns after clamping or implantation. The evidence base was dominated by prospective single-center feasibility studies with small to moderate sample sizes, and no randomized trials were identified. Conclusions: Clinical intraoperative HSI in abdominal surgery is a genuinely niche yet rapidly expanding topic with a sufficient number of human studies to support a relevant systematic review. Current evidence consistently supports feasibility, quantitative perfusion discrimination, and plausible intraoperative utility, especially in colorectal and transplant-related surgery. However, the field remains methodologically heterogeneous, and the next research priority is multicenter standardization with clinically anchored thresholds and outcome-driven comparative studies. Full article

Heart failure (HF) has traditionally been regarded as a primary myocardial disorder in veterinary medicine. However, accumulating evidence suggests that HF represents a systemic syndrome characterized by dynamic multiorgan interactions. In human cardiovascular research, cardiorenal and cardiointestinal paradigms have reshaped disease conceptualization, yet comparable integrative frameworks remain underdeveloped in veterinary cardiology. Naturally occurring canine HF—particularly myxomatous mitral valve disease and dilated cardiomyopathy—offers a clinically relevant translational platform in which systemic remodeling unfolds within an intact physiological lifespan. This review proposes a systems-based perspective that integrates spontaneous canine HF with controlled in vivo experimental models. We outline four main pathways of interaction: (1) the heart–gut axis, wherein reduced perfusion can influence inflammation and disruption of the intestinal barrier; (2) the heart–bone axis, wherein endocrine factors like osteoprotegerin and osteocrin can impact remodeling of the cardiovascular system; (3) the heart–vascular endothelium axis, wherein inflammatory signaling and dysfunction of the vascular endothelium are hallmarks; and (4) the neurocardiac axis, which reflects an imbalance in the autonomic nervous system. Emerging regenerative and organelle-based strategies—including mesenchymal stem cell therapy and mitochondrial transplantation—are discussed within this multiorgan framework. Rather than focusing solely on cardiac contractility, these approaches may function as systemic inflammatory modulators, and endothelial, metabolic, and autonomic pathways. Canine HF can be better understood as a multiorgan network condition; reframing it in this way can help researchers in the field of translational cardiology create more comprehensive diagnostic and treatment plans. Full article

Background/Objectives: Doxorubicin is an anthracycline chemotherapeutic agent widely used in the treatment of breast cancer. However, its clinical utility is limited by the drug’s resistance development, low oral bioavailability, and dose-dependent side effects. The semi-essential amino acid, L-arginine, has gained attention as a potential adjuvant that could improve the drug distribution and cytotoxic effectiveness of chemotherapeutics. This study aimed to explore the multifunctional effect of L-arginine on the intestinal absorption and anti-breast cancer activity of doxorubicin. Methods: The rabbit in situ intestinal perfusion technique was employed to investigate the membrane transport parameters of doxorubicin both in the absence and presence of L-arginine. Furthermore, the effect of L-arginine on the cytotoxic activity of doxorubicin against breast cancer cells (MCF-7) was assessed using the MTT assay. Results: Co-perfusion of L-arginine with doxorubicin enhanced the fraction of doxorubicin absorbed, with a recorded 4.3-fold enhancement in the jejuno-ileum and a 1.5-fold enhancement in the colon segment. In MCF-7 cells, co-treatment with L-arginine resulted in a significant potentiation of doxorubicin cytotoxicity. At L-arginine concentrations of 10 μM and 50 μM, the recorded IC₅₀ decreased from 41.3 μM to 8.2 μM and to 22.1 μM, respectively. The superior efficacy of 10 μM L-arginine compared to 50 μM reflected a biphasic concentration-dependent response. Conclusions: L-arginine modulated two critical aspects of doxorubicin efficacy, intestinal absorption and cytotoxic activity. The biphasic response emphasizes the importance of L-arginine dose optimization. These findings support the potential of L-arginine as a safe adjuvant for developing oral doxorubicin formulations. This approach can reduce the dose-related toxicity of doxorubicin and improve therapeutic outcomes. Full article

Ruminants can use volatile fatty acids from rumen fermentation for energy, but substantial starch may bypass the rumen and enter into the small intestine under a high-grain diet. In theory, intestinal starch digestion is energetically more efficient than ruminal fermentation. However, ruminants have inherent limits in starch hydrolysis and glucose transport. Small intestinal starch digestion relies on pancreatic α-amylase. Several studies have indicated that functional amino acids (Leu or Phe) may enhance amylase secretion or activity to improve starch digestion. In contrast, strategies to increase glucose absorption efficiency in the small intestine have received less attention. Thus, this review focuses on the effects of diet, ontogeny, environment, and intestinal microbiota on intestinal glucose absorption and their potential mechanisms. The T1R2/T1R3 glucose-sensing pathways, transporting pathways, and related hormones within the small intestine were systematically reviewed. The advantages and limitations of major approaches regarding glucose absorption including portal vein intubation, nutrient perfusion, everted intestinal sacs in vitro, Ussing chamber, brush-border membrane vesicle, D-xylose test, organoid, and nanosensing are also discussed. Importantly, we propose potential strategies to improve small intestinal glucose absorption (e.g., artificial sweeteners and glucagon-like peptide 2-related modulation). Overall, this review summarizes promising regulatory targets to enhance small intestinal glucose absorption and improve energy efficiency in ruminants. Full article

Objectives: Hypertension is common in Alzheimer’s disease (AD) and contributes to functional decline. While ACE inhibitors are widely used for hypertension, their systemic effects on intestinal permeability and physical capacity in AD patients remain unclear. Materials and Methods: We investigated the potential contribution of increased intestinal permeability to handgrip strength (HGS) and physical capacity in patients with Alzheimer’s disease (AD) taking ACE inhibitors. We investigated hypertensive AD patients taking ACE inhibitors (n = 55) or other anti-hypertensive medications (n = 57) at baseline and one year later, along with age-matched controls (n = 64) and normotensive AD patients (n = 61). We measured plasma zonulin, a marker of intestinal permeability, and HGS, and performed the short physical performance battery (SPPB). Results: AD patients had lower HGS, gait speed, SPPB, and higher plasma zonulin than controls at baseline (all p < 0.05). The use of ACE inhibitors was associated with increased HGS and gait speed, and reduced plasma zonulin in AD patients. Conversely, AD patients on other anti-hypertensive medications had higher zonulin and lower HGS but no change in gait speed and SPPB after one year. The patients taking ACE inhibitors also exhibited significant dynamic correlations of zonulin with HGS, gait speed, and SPPB (p < 0.05). ACE inhibitors also reduced plasma C-reactive proteins and 8-isoprostanes as markers of oxidative stress and inflammation. Conclusions: ACE inhibitors may improve physical performance and cognitive function in hypertensive AD patients, primarily through vascular smooth muscle modulation, leading to better perfusion. These effects may indirectly support intestinal barrier and muscle function, highlighting a novel gut–vascular–muscle interface relevant to therapeutic strategies. Full article

Background: Aortic arch reconstruction in neonates is often challenging, owning its surgical complexity and postoperative complication risk. To assess intestinal damage, we compared selective anterograde cerebral perfusion (SACP) and SACP with additional distal perfusion (SACP + DP) used in aortic arch surgery in a neonatal piglet model. Methods: Piglets underwent cardiac arrest for 60 min with SACP (n = 9) or SACP + DP (n = 9), followed by a 120 min recovery. Hemodynamic parameters, blood gases and electrolytes were monitored. Biopsies of the small intestine and colon were analyzed for histopathological changes, intestinal barrier function, and oxidative stress. Results: Hemodynamic measurements and electrolyte concentrations were comparable between SACP and SACP + DP (p > 0.05), except for potassium levels during cardiac arrest (p = 0.03). Blood lactate levels (p < 0.01) were elevated and pH values (p < 0.01) were reduced in the SACP group during cardiac arrest. Morphometric analysis of the intestinal tissue revealed longer crypts (p = 0.02) and a thicker mucosal layer (p = 0.05) of colonic structures in the SACP group. Compared to SACP, the mRNA expression of cytoprotective Parkinson’s disease protein DJ-1 (p = 0.02) and hypoxia-inducible nuclear factor erythroid 2-related factor 2 (p = 0.04) were higher in the small intestine of the SACP + DP group. The marker of epithelial barrier function, E-cadherin, showed lower mRNA expression in the colon of the SACP + DP group (p = 0.02). Conclusions: Our study results showed that SACP + DP revealed less intestinal tissue damage and loss of structural integrity, as well as an upregulation of cytoprotective molecules and anti-oxidative stress mechanisms. Therefore, SACP + DP is a reliable procedure in our model for aortic arch surgery that can contribute to better postoperative outcomes by reducing intestinal damage. Full article

The intestine–liver–muscle axis plays an essential role in drug and nutrient absorption, metabolism, and energy balance. Yet in vitro models capable of recapitulating this inter-organ communication remain limited. Here, we present a pump-free, 3D-printed multi-organ-on-a-chip device that enables dynamic co-culture of Caco-2 intestinal epithelial cells, HepG2 hepatocytes, and primary human skeletal myoblasts (HSkMs) under gravity-driven oscillatory flow. The device consists of five interconnected chambers designed to accommodate Transwell cell culture inserts for intestine and muscle compartments and hydrogel-embedded hepatocyte spheroids in the central hepatic compartment. The device was fabricated by low-cost fused deposition modeling (FDM) using acrylonitrile butadiene styrene (ABS) polymers. Under dynamic rocking, oscillatory perfusion promoted inter-organ communication without the need for external pumps or complex tubing. Biological assessments revealed that dynamic co-culture significantly enhanced the characteristics of skeletal muscle, as indicated by increased myosin heavy chain expression and elevated lactate production, while HepG2 spheroids exhibited improved hepatic function with higher albumin expression compared with monoculture. Additionally, Caco-2 cells maintained stable tight junctions and transepithelial electrical resistance, demonstrating preserved intestinal barrier integrity under dynamic flow. These results establish the device as a versatile, accessible 3D-printed platform for modeling the intestine–liver–muscle axis and investigating metabolic cross-talk in drug discovery and disease modeling. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder characterized by immune dysregulation, metabolic impairments, neuroendocrine disturbances, endothelial dysfunction, and gastrointestinal abnormalities. Immune alterations include reduced natural killer cell cytotoxicity, T-cell exhaustion, abnormal B-cell subsets, and the presence of diverse autoantibodies, suggesting an autoimmune component. Gut dysbiosis and increased intestinal permeability may promote systemic inflammation and contribute to neurocognitive symptoms via the gut–brain axis. Neuroendocrine findings such as hypothalamic–pituitary–adrenal (HPA) axis hypofunction and altered thyroid hormone metabolism further compound metabolic and immune abnormalities. Metabolomic and mitochondrial studies identify impaired ATP generation, redox imbalance, and compensatory shifts toward alternative energy pathways underlying hallmark symptoms like post-exertional malaise. Endothelial dysfunction driven by oxidative and nitrosative stress, along with autoantibody-mediated receptor interference, may explain orthostatic intolerance and impaired perfusion. Collectively, ME/CFS appears to arise from a self-sustaining cycle of chronic inflammation, metabolic insufficiency, and neuroimmune imbalance. Full article

Heart failure (HF) affects over 55 million individuals globally, with prevalence projected to exceed 11 million in the United States by 2050 and is increasingly recognized as a systemic disorder extending beyond hemodynamic dysfunction to encompass profound alterations in neural and gut physiology. Cognitive impairment affects nearly half of HF patients and represents a major determinant of morbidity, self-care capacity, and mortality. Recent advances suggest that the gut microbiome serves as a pivotal intermediary in the heart–brain crosstalk, influencing neurocognitive outcomes through inflammatory, metabolic, and neurohumoral pathways. Dysbiosis in HF disrupts intestinal barrier integrity, facilitating translocation of endotoxins and microbial metabolites such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids, which in turn modulate neuroinflammation, cerebral perfusion, and neuronal signaling. The gut–heart–brain axis provides an integrative framework linking HF and cognitive impairment pathophysiology through dysbiosis-driven systemic inflammation and metabolite dysregulation. Gut-derived biomarkers and microbiome-targeted interventions represent promising strategies for detection of early alterations and precision treatment, highlighting the urge for prospective, multi-omics studies to establish causality and therapeutic efficacy. This review synthesizes current evidence connecting gut microbiome dysbiosis and metabolite alterations to both HF and cognitive impairment pathophysiology and proposes translational strategies for integrating microbiome-targeted therapies in HF patients with cognitive dysfunction. Full article

Sinomenine (SIN), as a potential therapeutic agent for rheumatoid arthritis (RA), exhibits advantages such as non-addictiveness. However, its low aqueous solubility and poor membrane permeability result in limited bioavailability, which compromises its therapeutic efficacy in conventional formulations. To address these limitations, this study developed nanostructured lipid carriers (NLCs) with optimized formulations and evaluated their pharmacodynamic performance. Molecular dynamics (MD) simulations were employed to screen excipients and analyze the blending system. SIN-loaded NLCs (SIN-NLCs) were prepared using high-pressure homogenization. Single-factor experiments were performed to optimize the processing conditions of SIN-NLCs. A three-factor, three-level experimental design was established using Design Expert 13 software and further refined through Box–Behnken design (BBD) response surface methodology. This approach enabled cross-validation between molecular dynamics simulations and conventional experiments. Additionally, transmission electron microscopy (TEM) was used to examine morphology, while X-ray diffraction analysis (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR) were employed to characterize the physicochemical state of SIN in NLCs. Pharmacodynamic evaluation was performed in a RA model, supplemented by single-pass intestinal perfusion study (SPIP). Initially, MD simulations were employed to evaluate drug–excipient compatibility, thereby identifying suitable formulation excipients: stearic acid and oleic acid as lipid components, and Poloxamer 188 as the surfactant. Subsequently, single-factor experiments combined with the BBD response surface methodology were employed to optimize preparation parameters, establishing the ideal process conditions: drug-to-lipid ratio of 1:42, solid-to-liquid lipid ratio of 5.58:4.42, and Poloxamer 188 concentration of 1.20%. The optimized SIN-NLCs exhibited spherical particles with uniform dispersion and no agglomeration. The average particle size was 173.90 ± 1.97 nm, with a polydispersity index (PDI) of 0.18 ± 0.01, a zeta potential of −22.65 ± 0.60 mV, and an encapsulation efficiency (EE%) of 91.27% ± 0.01. Spectroscopic analysis confirmed that SIN existed in an amorphous state and was successfully encapsulated within the lipid matrix. In vivo, SIN-NLCs significantly reduced paw swelling and arthritis scores in model rats, promoted synovial cell proliferation, and suppressed inflammatory cell infiltration. The intestinal perfusion study demonstrated that SIN-NLCs were primarily absorbed in the small intestine and markedly enhanced drug permeability. SIN-NLCs represent an effective delivery system to enhance the solubility and permeability of SIN. This study provides a novel strategy and methodology for the formulation of hydrophobic drugs, offering valuable insights for future pharmaceutical development. Full article

The operative management of complex abdominal wall hernias in nonagenarians entails significant risk, with emergent repair associated with mortality rates approaching 40%. We report the case of a functionally independent 90-year-old male presenting with a 48 h history of abdominal pain, obstipation, and emesis, consistent with an acute-on-chronic incarcerated ventral hernia. Despite advanced age and elevated perioperative risk, multidisciplinary evaluation supported surgical intervention. Laparotomy revealed a 22 × 18 cm hernia sac harboring an elongated sigmoid and approximately 150 cm of small intestine with signs of compromised perfusion secondary to an internal constriction band. Following adhesiolysis and decompression, bowel viability was restored, and a mesh repair was performed. The postoperative course was notable for transient respiratory failure necessitating reintubation and ICU management; however, full recovery was achieved by one-month follow-up. This case demonstrates that comprehensive assessment, rather than chronological age, should guide operative decision-making in nonagenarians and underscores the feasibility of complex abdominal wall reconstruction in this cohort when supported by multidisciplinary care and perioperative resources. Full article

Sinomenine (SIN) is a promising candidate for the treatment of rheumatoid arthritis (RA). Although it possesses the advantage of being non-addictive, its poor aqueous solubility and low oral bioavailability have limited its clinical application. To address these issues, SIN was encapsulated into lipid cubic liquid crystal nanoparticles (LCNPs) and systematically characterized. Molecular dynamics (MD) simulations were first employed to screen suitable excipients for formulation development. Combined with single-factor optimization and Box–Behnken response surface design, the optimal composition and preparation process were determined. The resulting SIN-LCNPs exhibited a particle size of 149.7 ± 0.9 nm, a polydispersity index (PDI) of 0.223 ± 0.01, a zeta potential of −18.9 mV, and an encapsulation efficiency (EE%) of 92.2%. Spectroscopic analyses confirmed successful incorporation of SIN into the lipid matrix. Pharmacodynamic studies revealed that SIN-LCNPs enhanced targeted drug delivery to inflamed joints, significantly alleviating inflammation and suppressing disease progression in rats. In vivo single-pass intestinal perfusion (SPIP) experiments further demonstrated that SIN was primarily absorbed through the small intestine and that the LCNP carrier effectively improved its intestinal permeability. Collectively, this study provides a novel strategy and theoretical foundation for developing efficient formulations of poorly water-soluble drugs, highlighting the potential clinical application of SIN-LCNPs in RA therapy. Full article

Microphysiological systems (MPSs) have emerged as alternatives to animal testing in drug development, following the FDA Modernization Act 2.0. Double-layer channel-type MPS chips with porous membranes are widely used for modeling various organs, including the intestines, blood–brain barrier, renal tubules, and lungs. However, these chips faced challenges owing to optical interference caused by light scattering from the porous membrane, which hinders cell observation. Trans-epithelial electrical resistance (TEER) measurement offers a non-invasive method for assessing barrier integrity in these chips. However, existing electrode-integrated MPS chips for TEER measurement have non-uniform current densities, leading to compromised measurement accuracy. Additionally, chips made from polydimethylsiloxane have been associated with drug absorption issues. This study developed an electrode-integrated MPS chip for TEER measurement with a uniform current distribution and minimal drug absorption. Through a finite element method simulation, electrode patterns were optimized and incorporated into a polyethylene terephthalate (PET)-based chip. The device was fabricated by laminating PET films, porous membranes, and patterned gold electrodes. The chip’s performance was evaluated using a perfused Caco-2 intestinal model. TEER levels increased and peaked on day 5 when cells formed a monolayer, and then they decreased with the development of villi-like structures. Concurrently, capacitance increased, indicating microvilli formation. Exposure to staurosporine resulted in a dose-dependent reduction in TEER, which was validated by immunostaining, indicating a disruption of the tight junction. This study presents a TEER measurement MPS platform with a uniform current density and reduced drug absorption, thereby enhancing TEER measurement reliability. This system effectively monitors barrier integrity and drug responses, demonstrating its potential for non-animal drug-testing applications. Full article