Infection Inflammation Research Articles

TIGIT-expression on natural killer cell subsets is an early indicator of alleviating liver inflammation following bulevirtide treatment in chronic hepatitis D.

Bulevirtide (BLV) is a novel and the only approved treatment option for patients with chronic hepatitis D (CHD). BLV alleviates liver inflammation already early during treatment when only minor HDV RNA changes are observed. We hypothesized that BLV-treatment may influence immune cells in CHD patients and performed a high-resolution analysis of natural killer (NK) cells before and during BLV-therapy. BLV-treated CHD patients (n=20) from a single-center cohort were longitudinally analyzed for clinical, molecular, and virological parameters. Peripheral blood mononuclear cells (PBMCs) were studied at baseline (BL), therapy weeks 3 (TW3) and 48 (TW48) by spectral flow cytometry. Healthy donors (HD), chronic hepatitis C (CHC) patients after direct-acting antivirals (DAA)-treatment and patients with chronic hepatitis B (CHB) were used as controls. Overall NK cell frequencies remained stable during BLV-treatment. However, biochemical responders (BR) showed distinct NK cell immunophenotypic features before and during therapy. TIGIT-expression increased on CD56dim and CD56bright NK cells during the course of BLV-treatment and inversely correlated with alanine aminotransferase (ALT) levels in CHD but not CHC or CHB patients. High frequencies of TIGIT- CD57+ CD56dim NK cells at BL and low levels during therapy were indicative of a biochemical response. We here suggest that lacking the expression of the immune checkpoint inhibitor TIGIT on NK cell subtypes may be a hallmark of liver inflammation in HDV infection. BLV-therapy is associated with a reappearance of TIGIT on these cells, which may be one mechanism of why liver enzymes rapidly improve during therapy.

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

Antibacterial and Anti-Inflammation Activity of Titanium Alloy by Efficient Copper Immobilization.

Titanium alloy plates are often used for fixation to bone. However, the plates often need to be removed due to infection and adverse inflammation. To avoid these problems, we immobilized copper, which has antibacterial effects and low cytotoxicity, on titanium plates by immersing the titanium in copper-tris(hydroxymethyl)aminomethane complex solutions. The amount of copper immobilized on the titanium alloy surface was dependent on the amount of tris(hydroxymethyl)aminomethane and the pH of the solutions. The maximum amount of copper immobilized on the titanium alloy surface was about 20 atomic%, without any change in the surface morphological characteristics. The obtained titanium alloy with immobilized copper exhibited antibacterial and anti-inflammation properties without cytotoxicity.

Deficient neutrophil responses early in influenza infection promote viral replication and pulmonary inflammation.

Neutrophils play key protective roles in influenza infections, yet excessive neutrophilic inflammation is a hallmark of acute lung injury during severe infections. Phenotypic heterogeneity is increasingly recognized in neutrophil populations; however, how functional variation in neutrophils between individuals determine the diverse outcomes of influenza remains unclear. To examine immunologic responses that may drive varying outcomes in influenza, we infected C57BL/6 (B6) and A/J mice with mouse-adapted influenza A virus A/PR/8/34 H1N1. A self-resolving dose in B6 mice was lethal in A/J mice, which had increased viral load throughout infection accompanied by prominent bronchoalveolar neutrophilia and pulmonary vascular leakage preceding mortality. Notably, the B6 mice heavily recruited neutrophils to lungs early in infection while A/J mice failed to do so. Neutrophils from A/J mice additionally displayed reduced neutrophil extracellular trap (NET) release and reactive oxygen species (ROS) generation compared to B6 mice early in infection, suggesting the failure to control virus in A/J mice was a product of deficient neutrophil response. To determine if variation in neutrophils between strains governed viral control and inflammation, we adoptively transferred bone marrow neutrophils from B6 or A/J donors to A/J recipients early in infection and found that the transfer of B6 neutrophils enhanced viral clearance and abrogated the dissemination of CXCL1 and IL-6. The transfer of A/J neutrophils, however, failed to achieve either. Furthermore, B6 neutrophils were capable of greater levels of viral killing in vitro than their A/J counterparts. These results suggest that a key moderator of inflammation in influenza infection is the control of virus by neutrophils early in infection. Thus, host-specific differences in both the recruitment of these cells as well as interindividual variation in neutrophil ability to support viral clearance may in part dictate differing susceptibility to respiratory viral infections.

Traditional uses, botanical description, phytochemistry, and pharmacological activities of Phytolacca acinosa: a review.

Phytolacca acinosa is an herbaceous herb belonging to the Phytolaccaceae family. The plant has a long history of usage in traditional medicine for treating a variety of ailments including infectious diseases, edema, inflammation, gastric, and abdominal distress. The traditional use, phytochemistry, and pharmacological properties of Phytolacca acinosa are outlined in this article. To date, few bioactive molecules have been identified and isolated from the plant, such as phytolacacinoside A, esculentoside H, jaligonic acid and esculentoside B, phytolaccanol and epiacetyl aleuritolic acid, esculentoside A, esculentoside C, esculentoside D, esculentoside T, esculentoside S, sitosterol. The literature related some of the reported ethnomedicinal uses of the plant to these compounds found in different parts of the plant. The in-depth knowledge about the significance of Phytolacca acinosa presented in this review may open up opportunities for research development in drug discovery and a better comprehension of the therapeutic advantages of the plant.

Atomic-layer-deposition application for antibacterial coating of biomedical materials: surgical sutures.

Suture-associated surgical site infection (SSI) causes bacterial pathogens to colonize on the suture surface that are highly resistant to antibiotic treatment. Conventional suture materials used in surgical practice are causing complications such as infection and chronic inflammation. Surgical suture materials with antibacterial coatings are widely used in surgical practice. The surgical sutures based on antibacterial nanomaterials possess a more promising efficacy. The antibacterial coatings can make a significant contribution to prevention of suture-associated SSI. In the present work, we proposed a new method of antibacterial coating of the surgical sutures based on the atomic layer deposition (ALD) technique. The main aim of the present work is to use the V-doped TiO2 thin film synthesized based on ALD technology, on the surface of the surgical suture to enhance its antibacterial activity for treatment of the SSI. Surgical sutures with enhanced antibacterial activity have been developed using ALD method to prevent microbial colonization of the suture material in operative incisions. The ALD experiment was performed at a temperature of 85 °C using super-cycles of self-saturating hydrolysis reactions between TiCl4 and H2O, VOCl3 and H2O precursors. Antimicrobial properties of TiVOx coated sutures were studied against two types of microorganisms, Escherichia coli (E. coli) and Proteus vulgaris (Pr. Vulgaris). We demonstrate the application of ALD as a technique to synthesize nanoscale coatings on surgical suture (polypropylene, surgical suture material, non-absorbable monofilament Ethicon Prolene 2-0). We found that the coated sutures illustrated high stability. Surgical sutures coated with an antibacterial agent (TiVOx) proposed in this work based on ALD technique provide a novel approach to preparing multifunctional sutures and significantly reducing inflammatory reactions and improving wound healing. The efficiency of the derived TiVOx -coated sutures was tested on small animals for comparative analysis of the use of coated and uncoated PP sutures to prevent SSI.

G protein-coupled purinergic P2Y receptors in infectious diseases.

The purinergic P2Y receptors comprise eight G-coupled receptor (GPCR) subtypes already identified (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12-14). P2Y receptor physiological agonists are extracellular purine and pyrimidine nucleotides such as ATP (Adenosine triphosphate), ADP (Adenosine diphosphate), UTP (Uridine triphosphate), UDP (Uridine diphosphate), and UDP-glucose. These receptors are expressed in almost all cells. P2Y receptors are found in immune cells, such as macrophages, neutrophils, mast cells, dendritic cells, and lymphocytes. P2Y receptors play essential roles in inflammation and are involved in several cell processes, including efferocytosis, phagocytosis, chemotaxis, degranulation, killing pathogens, cytokine production, and platelet aggregation. These processes underpin immune responses against pathogens. Therefore, here we discuss P2Y receptor pharmacology and mechanisms triggered by the activation of these receptors in virus, bacteria, and parasite infections. In addition, we highlight the therapeutical potential of P2Y receptors for developing new pharmacological strategies to modulate inflammation and disease outcomes in pathogen infections.

Association of environmental pollutants with asthma and allergy, and the mediating role of oxidative stress and immune markers in adolescents

BackgroundAsthma and allergic diseases are among the common causes of morbidity and mortality globally. Various environmental pollutants are linked to the development of asthma and allergic diseases. Evidence on the role of oxidative stress and immune markers in the association of environmental pollutants with asthma and allergy is scant. We examined cross-sectional associations between environmental pollutants and asthma and allergy, investigated mixture effects and possible mediation by oxidative stress or immune markers. MethodsWe used data from the Flemish Environment and Health Study 2016–2020 (FLEHS IV), including 409 adolescents aged 13 to 16 years. Fifty-four pollutants, including metals, phthalates, Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), bisphenols, currently used and legacy pesticides, flame retardants, per- and polyfluoroalkyl substances (PFAS), polyaromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were analyzed. Outcomes were self-reported asthma, rhinitis, eczema, allergies, respiratory infection, and airway inflammation, measured through fractional exhaled nitric oxide (FeNO). Single pollutant models using multiple regression analysis and multipollutant models using Bayesian Kernel Machine Regression (BKMR) were fitted. As sensitivity analysis, Bayesian model averaging (BMA) and elastic net (ENET) models were also performed. For Bayesian models, posterior inclusion probabilities (PIP) were used to identify the most important chemicals. Mediation analysis was performed to investigate the role of oxidative stress, measured by urinary 8-hydroxy-2' -deoxyguanosine (8-OHdG), and immune markers (eosinophils, basophils, InterLeukin8, InterLeukin6, and Interferon-ᵧ in blood). ResultsIn single pollutant models, FeNO was significantly higher by 20% (95% CI: 6, 36%) and 13% (95% CI: 2, 25%) per interquartile range (IQR) fold in mono-n-butyl phthalate (MnBP) and mono-benzyl phthalate (MBzP), respectively. In BKMR analysis, the group PIPs indicated phthalates and DINCH as the most important group (group PIP=0.509), with MnBP being the most important pollutant within that group (conditional PIP=0.564; %change=28%; 95%CI: 6, 54%). Similar patterns were observed in all multipollutant models. Eosinophil count mediated 37.8% (p=0.018) and 27.9% (p=0.045) of the association between MBzP and FeNO, and the association between MnBP and FeNO, respectively. 8-OHdG plays a significant mediating role in the association of 2,4-Dichlorophenoxyacetic acid (2,4-D) (55.4%), 3,5,6-Trichloro-2-pyridinol (TCPY) (48.1%), and 1-Naphthylamine (1-NAP) (32.7%) with rhinitis, while the total effects of these chemicals on rhinitis were not statistically significant. ConclusionsThis study found associations between phthalates, MnBP and MBzP, and elevated FeNO, which appeared to be mediated by eosinophil count. 8-OHdG plays a significant mediating role in the association between 2,4-D, TCPY, and 1-NAP with rhinitis, while their direct effects remain non-significant. Use of inflammatory and oxidative stress markers can enhance the understanding of inflammatory processes in asthma and allergic diseases due to environmental pollutants.

Daptomycin alleviates collagen-induced arthritis via suppressing inflammatory cytokines and NF-κB pathway.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, and its pathogenic factors include bacterial infection and immune inflammation. Daptomycin (DAP) is a cyclic lipopeptide that has been approved to treat skin infections, bacteremia and right-sided endocarditis due to its effective antibacterial effects against most Gram-positive pathogenic bacteria. Herein, we focus on whether DAP exerts anti-inflammatory activity on RA to expand DAP drug indications. Our studies are first time to evaluate anti-inflammatory effect and reveal its molecular pharmacological mechanism of DAP on lipopolysaccharide-activated macrophage and collagen-induced arthritis (CIA) mice. In vitro cytological studies show that 10µg/mL DAP inhibits secretion of IL-1β, IL-6 and TNF-α to alleviate cell inflammation, and the phosphorylation level of p65 (p-p65) of RAW 264.7 cells is decreased under DAP exposure. Administration with 10mg/kg/2d DAP via intravenous injection on CIA mice significantly reduces arthritis symptom by inhibiting p-p65 level and decreasing serum level of IL-6, IL-1β and TNF-α. Moreover, our study is the first time to reveal new immunomodulatory effects of DAP on RA, which provides a pharmacological basis for new clinical applications of DAP for other immune-related diseases except to bacterial infections.

Through a Hazy Lens: A Teen’s Surprising Struggle with Juvenile Cataracts

A juvenile cataract is a condition in which the eye's lens gets cloudy, affecting children and teenagers and considerably impairing vision. It accounts for approximately 5% to 20% of childhood blindness worldwide. A 16-year-old male patient came with his parents to the Pediatric Ophthalmology and Strabismus Department of RSUD dr. Zainoel Abidin with complaints of blurred vision in both eyes. The patient admitted that his visual acuity was deteriorating, and he had difficulty seeing the blackboard when the teacher explained it at school. There were no factors that aggravated or relieved the patient's complaints. The ophthalmologic examination showed the visual acuity of both eyes was 6/30, and the bilateral lenses were opaque. The patient was diagnosed with juvenile cataract oculi dextra et sinistra. Subsequently, the patient was planned for aspiration irrigation with intraocular lens (IOL) insertion in both eyes, membranectomy, primary posterior capsulectomy (PPC), and anterior vitrectomy (AV). Following the surgery, the visual acuity of both his eyes was improved to 6/7 and 6/10. The patient was also prescribed oral and topical antibiotics and topical anti-inflammatories to prevent infection and persistent inflammation after surgery. After surgery, the patient was also planned for optical rehabilitation one month postoperatively by being prescribed glasses with the best correction of 6/6 in both eyes.

Pharmacological blockade of infection chronification modulates oxy-inflammation and prevents the activation of stress-induced premature senescence markers in schistosomiasis.

Chronic inflammation, oxidative stress, and DNA damage are observed in schistosomiasis and premature aging. However, the potential of these events to trigger stress-induced premature senescence (SIPS) throughout schistosomiasis progression remains overlooked, especially in response to the first-line pharmacological treatment. Thus, we investigated the relationship between oxidative stress and SIPS sentinel markers in untreated Schistosoma mansoni-infected mice and those receiving praziquantel (Pz)-based reference treatment. Swiss mice were randomized into 5 groups: uninfected (followed by 60- and 180-days post-infection), acutely (60 days) and chronically (180 days) infected untreated, and infected treated with Pz followed until 180 days. Our results indicated that infection chronification was accompanied by the worsening of hepatic granulomatous inflammation, increased number of granulomas, IL-4, TGF-β, reactive oxygen species (ROS) levels, fibrosis, hepatocytes DNA damage, upregulation in SA-β-gal activity, p16 and p21 gene expression, and hepatocytes proliferation down-regulation in the absence of telomeric shortening. These abnormalities were blocked by Pz treatment, which prevented infection chronification and the decline in hepatocytes proliferative potential, stimulating granulomatous inflammation resolution. Taken together, our findings provide the evidence that progressive fibrosis, sustained production of high ROS levels, marked DNA damage and decline in p16 and p21 expression are associated with hepatocytes replication attenuation in the chronic phase of S. mansoni infection. Thus, pharmacological blockade of infection and granulomatous inflammation is essential to prevent these premature senescence markers associated with hepatocytes replicative disorders, stimulating liver regeneration in schistosomiasis mansoni.

RELATIONSHIP BETWEEN ANEMIA, CRP AND HELICOBACTER PYLORI IN ELDERLY MALE POPULATION

Background: Anemia is a prevalent medical condition in elderly populations, contributing significantly to morbidity and healthcare burden globally. Helicobacter pylori (H. pylori) infection and systemic inflammation, indicated by elevated C-reactive protein (CRP), are potential contributors to anemia. Understanding the relationship between anemia, H. pylori, and CRP in elderly males can enhance diagnostic and therapeutic strategies, particularly in resource-limited settings where these conditions are highly prevalent. Objective: To determine the association between anemia, CRP levels, and H. pylori infection in elderly males. Methods: This cross-sectional observational study was conducted over six months from January 1 to June 30, 2023, at a tertiary care hospital in Rawalpindi. A total of 300 male participants aged above 65 years were recruited. After informed consent, 2cc venous blood samples were collected and analyzed for hemoglobin levels, red blood cell indices, and CRP-Q levels using Sysmex XP-100 and Beckman Coulter automated analyzers. Stool samples were tested for H. pylori antigen using the H. PYLORI QUIK CHEK enzymatic immunoassay. Data were statistically analyzed using SPSS version 22. Results: Out of 300 participants, 270 (90%) were anemic, with 90 (33.3%) classified as mild anemia, 145 (53.7%) as moderate, and 35 (12.9%) as severe anemia. Microcytic anemia was the most common subtype (60.7%), with 158 (96.3%) of the 164 microcytic anemia cases testing positive for H. pylori. CRP-Q was elevated in 237 (87.7%) individuals, with a strong correlation observed between elevated CRP levels, H. pylori positivity, and microcytic anemia. H. pylori stool antigen was positive in 242 (89%) participants, particularly among those with anemia. Conclusion: This study highlights a strong association between anemia, H. pylori infection, and CRP levels in elderly males, emphasizing the importance of addressing H. pylori infection as part of anemia management in this population.

Chronic inflammation degrades CD4 T cell immunity to prior vaccines in treated HIV infection

To date, our understanding of how HIV infection impacts vaccine-induced cellular immunity is limited. Here, we investigate inflammation, immune activation and antigen-specific T cell responses in HIV-uninfected and antiretroviral-treated HIV-infected people. Our findings highlight lower recall responses of antigen-specific CD4 T cells that correlate with high plasma cytokines levels, T cell hyperactivation and an altered composition of the T subsets enriched with more differentiated cells in the HIV-infected group. Transcriptomic analysis reveals that antigen-specific CD4 T cells of the HIV-infected group have a reduced expression of gene sets previously reported to correlate with vaccine-induced pathogen-specific protective immunity and further identifies a consistent impairment of the IFNα and IFNγ response pathways as mechanism for the functional loss of recall CD4 T cell responses in antiretroviral-treated people. Lastly, in vitro treatment with drugs that reduce inflammation results in higher memory CD4 T cell IFNγ responses. Together, our findings suggest that vaccine-induced cellular immunity may benefit from strategies to counteract inflammation in HIV infection.

Exploring the impact of tobacco consumption on the respiratory health of two Dutch skeletal populations (1300–1829 CE)

ABSTRACT This study explored the influence of tobacco consumption on the respiratory health of two historical Dutch populations (1300–1829 CE). We conducted a macroscopic examination of 235 skeletons for which tobacco consumption status was known, focusing on the presence of sinusitis, ear infection, and pulmonary inflammation. Our goal was to investigate the correlation between respiratory diseases and tobacco consumption. Despite all conditions being prevalent in the total sample (sinusitis: 50.2%, ear infection: 23.2%, pulmonary inflammation: 14.1%), almost no significant correlation was found between disease and tobacco consumption. Our findings suggest that additional factors, such as exposure to second-hand smoke and unsanitary living/working environments, may have also impacted respiratory health. However, our interpretations are difficult to confirm due to the limitations of macroscopic analysis in determining tobacco consumption status. Future research should consider employing biomolecular techniques and expand beyond respiratory diseases to enhance our understanding of historical health implications of tobacco use.

β-Defensin versus conventional markers of inflammation in periprosthetic joint infection: a retrospective study.

Diagnosing periprosthetic joint infection (PJI) remains a significant challenge for healthcare professionals. Commonly utilized inflammatory markers include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cells (WBC). Human β-defensin 1 (β-defensin) is an antimicrobial peptide elevated in infection, yet its diagnostic value for PJI has not been explored. The purpose of this study was to evaluate the efficacy of synovial β-defensin as a diagnostic marker for PJI and to compare its performance with ESR, serum CRP, and WBC. We conducted a single-center retrospective study from October 2022 to June 2023. A total of 105 joint fluid samples from revision patients at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra were collected intraoperatively (71 hips, 34 knees) and frozen. According to MSIS criteria, 64 patients were defined as positive for PJI and the remaining 41 were negative. Synovial β-defensin levels were quantified using ELISA, serum CRP levels by immunoturbidimetry, and blood ESR and WBC were analyzed. Sensitivity and specificity were determined using ROC curves, and diagnostic performance was compared using the area under the curve (AUC). Cut-off values for diagnosing PJI were established. Levels of synovial β-defensin, ESR, serum CRP, and WBC were significantly higher in the PJI group compared to the non-PJI (P<0.0001). The AUCs were 0.948 for β-defensin, 0.884 for ESR, 0.902 for CRP, and 0.767 for WBC, with a combined AUC of 0.994. Sensitivity/specificity for β-defensin, ESR, CRP, and WBC were 0.966/0.830, 0.887/0.791, 0.930/0.771, and 0.820/0.682, respectively. Optimal predictive cut-off values were 1105.8 pg/mL for β-defensin, 11.5 mm/h for ESR, 5.55 mg/L for CRP, and 7.3 × 103/mm3 for WBC. The synovial β-defensin assay demonstrated greater sensitivity and specificity for the diagnosis of PJI compared to ESR, serum CRP and WBC. Therefore, β-defensin shows promise as a diagnostic marker for PJI. Simultaneous determination of all markers may increase diagnostic confidence.

Polymer- and Lipid-Based Nanostructures Serving Wound Healing Applications: A Review.

Management of hard-to-heal wounds often requires specialized care that surpasses the capabilities of conventional treatments. Even the most advanced commercial products lack the functionality to meet the needs of hard-to-heal wounds, especially those complicated by active infection, extreme bleeding, and chronic inflammation. The review explores how supramolecular nanovesicles and nanoparticles-such as dendrimers, micelles, polymersomes, and lipid-based nanocarriers-can be key to introducing advanced wound healing and monitoring properties to address the complex needs of hard-to-heal wounds. Their potential to enable advanced functions essential for next-generation wound healing products-such as hemostatic functions, transdermal penetration, macrophage polarization, targeted delivery, and controlled release of active pharmaceutical ingredients (antibiotics, gaseous products, anti-inflammatory drugs, growth factors)-is discussed via an extensive overview of the recent reports. These studies highlight that the integration of supramolecular systems in wound care is crucial for advancing toward a new generation of wound healing products and addressing significant gaps in current wound management practices. Current strategies and potential improvements regarding personalized therapies, transdermal delivery, and the promising critically evaluated but underexplored polymer-based nanovesicles, including polymersomes and proteinosomes, for wound healing.

Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities.

Tertiary lymphoid structures (TLS)are accumulations of lymphoid cells that arise in ectopic sites through the process of lymphoid neogenesis in chronic inflammation in autoimmunity, microbial infections, organ rejection, aging, and cancer. Their cellular composition and function and regulation via members of the lymphotoxin (LT)/tumor necrosis factor (TNF) family resemble that of secondary lymphoid organs (SLOs). Tumor-associated (TA)-TLS can be associated with favorable clinical outcomes. Immunotherapy in the form of immune checkpoint inhibitors (ICI) has contributed to tremendous advances in cancer therapy. However, ICI are effective in only some tumors, can give rise to resistance, and can precipitate immune-related adverse events (irAEs), many of which appear to have hallmarks of autoimmunity and can resemble TLS. TA-TLS correlate with a positive response to immunotherapy, but they can also be associated with susceptibility to irAEs, suggesting that TA-TLS in combination with ICI could lead to uncontrolled autoimmunity. The tumor environment can be manipulated to ensure that, not only the number of TLS, but also their cellular composition and appropriate function allow for judicious combinations of TLS and immunotherapy that can synergize and contribute to better outcomes with a minimum of destructive irAEs. Strategies include directed delivery of lymphoneogenic cytokines and chemokines or vascular growth factors directly, via transgenes or via adenovirus vectors.

Licochalcone A loaded multifunctional chitosan hyaluronic acid hydrogel with antibacterial and inflammatory regulating effects to promote wound healing

The wound healing process is characterized by persistent infection and long-term inflammation. The licochalcone A (LicA) has the potential for skin wound healing and needs a good drug-loading platform to apply its antibacterial and anti-inflammatory effects. In this study, the LicA@chitosan (CS) -hyaluronic acid (HA) hydrogel with antibacterial and anti-inflammatory was developed for wound healing in mice. The SEM displayed that the hydrogel had an obvious porous structure and was very suitable to be used as a delivery carrier for LicA. The FTIR results suggested that the LicA can be effectively loaded in the CS-HA hydrogel. Variable strain scanning, frequency scanning and temperature scanning indicated that the LicA@CS-HA hydrogel can maintain the gel state. The LicA@CS-HA hydrogel had good biological safety, can inhibit the activity of Escherichia coli and Staphylococcus aureus, and can release LicA stably. The LicA@CS-HA hydrogel also has good adhesion and hemostatic properties. Finally, the LicA@CS-HA hydrogel significantly accelerated wound healing in mice skin injury model, and reduced inflammation and orderly collagen deposition were observed by HE and Masson staining. The immunohistochemistry indicated that the LicA@CS-HA hydrogel induced the positive expression of CD31, VEGF, and HIF-1α promoted neovascularization. The LicA@CS-HA hydrogel also down-regulated the expression of M1 macrophage markers CD86, IL-6, and TNF-α, and increased the expression of M2 macrophage markers CD206, IL-4, and IL-10 proteins. The molecular docking demonstrated that the target proteins had better binding activity to LicA. Collectively, the LicA@CS-HA hydrogel has broad application prospects in promoting wound healing.

A versatile natural gelatin-based hydrogel for emergency wound treatment through hemostasis, antibacterial, and anti-inflammation

Emergency wounds are often accompanied by bacterial infection, oxidative stress, and excessive inflammation due to the inability to quickly close and stop bleeding, resulting in chronic wounds that are difficult to heal. Clinically, surgical suturing is the fastest method for wound closure, but it is only suitable for wounds with small bleeding volumes and causes unsightly scar formation. Consequently, there is a critical need for hemostatic dressings versatile enough to address a spectrum of diverse and intricate wounds, especially in emergency scenarios. In this study, we constructed a unique versatile natural gelatin-based hydrogel with hemostasis, antibacterial, and anti-inflammation properties. The hydrogel was composed of 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butyrylethylenediamine-modified methacrylated gelatin (GelMA-NB) and epigallocatechin gallate-grafted polylysine (EPL-EGCG), which imparts adhesion, antibacterial and antioxidant properties to the hydrogel. Simultaneously, the hydrogel was loaded with GelMA microspheres encapsulating natural resveratrol (RES@GM). This combination not only exhibited outstanding hemostatic capabilities but also preserved the anti-inflammatory potential of RES. In different animal models, the hydrogel exhibited outstanding hemostatic and wound healing effects, down-regulated the expression of IL-1βto promote inflammatory regulation and potential for angiogenesis and anti-scar. In conclusion, unique versatile natural gelatin-based hydrogel suitable for various complex wounds provides a promising strategy for emergency wound dressing applications.

Detection of C-reactive protein using a label-free NIR fluorescent aptasensor with a large Stokes shift based on an AIEE anthracene derivative

BackgroundC-reactive protein (CRP), one of the classic biomarkers of inflammation, is closely related to infectious inflammation, cardiovascular disease, cancer, and other diseases. Therefore, timely and accurate detection of CRP in human blood is crucial for the discovery, diagnosis, and treatment of the aforementioned diseases. Herein, a novel label-free NIR fluorescence aptasensor with a large Stokes shift based on an AIEE anthracene derivative B and a molybdenum disulfide (MoS2) platform was developed and used for the high sensitivity and specificity detection of CRP. ResultsCompound B could emit near-infrared (NIR) fluorescence with a large Stokes shift (190 nm). Notably, this compound could bind with the aptamer of CRP (CRP-Apt) through electrostatic attraction to form a B/CRP-Apt complex, generating an aggregation-induced emission enhancement effect and enhancing the fluorescent intensity of B. B/CRP-Apt could be adsorbed on the surface of MoS2 with the addition of MoS2 to its solution, and the fluorescence of Compound B was quenched. CRP was then added to the above solution. CRP-Apt had a substantially higher affinity for CRP than MoS2. Therefore, B/CRP-Apt detached from the surface of MoS2 and bound to CRP, thereby restoring the fluorescence of B. Experimental results showed a good linear relationship between the fluorescent recovery intensity of B and the concentration of CRP in the concentration range of 0.3–70 ng mL−1, with a limit of detection as low as 0.1 ng mL−1. Significance and noveltyThe aptasensor integrates the advantages of high sensitivity of NIR fluorescence, high specificity of aptamers, good water-solubility and AIEE effect of Compound B. And it could be applied to the determination of CRP in human serum samples, while most of the reported methods can only determine CRP in spiked human serum samples.