Reduce Tissue Damage Research Articles

Mechanical effects of needle texture on acupoint tissue

ObjectiveThis study aims to clarify how the stimulation of acupuncture points is achieved by needles with different surface texture during acupuncture; it also seeks to lessen injury at the insertion site and increase the therapeutic efficacy of acupuncture, by simulating the mechanical effects of various needle surface patterns on Zusanli (ST36) without changing the radius of acupuncture needles. MethodsFive acupuncture needle models with different surface patterns, including the smooth needle, the lined needle, the ringed needle, the left-hand threaded needle and the right-hand threaded needle, and a layered model of the Zusanli acupoint were used to investigate how to reduce tissue damage and increase stimulation during acupuncture treatment. Puncturing of the skin as well as lifting-inserting and twisting needle manipulations were simulated using these models, and the degree of damage and force of stimulation caused by the acupuncture needles with different surface patterns during acupuncture were compared. ResultsThe smooth needle and the lined needle caused the least tissue damage during insertion, while the left-hand threaded and the right-hand threaded needles caused the most damage. The ringed needle, the left-hand threaded needle and the right-hand threaded needle stimulated the acupoint tissue more during lifting-inserting manipulations, while the lined needle and the smooth needle produced less stimulation. The stimulation of the lined needle on the acupoint tissue was the largest during twisting manipulation, whereas the left-hand threaded needle and the right-hand threaded needle had smaller effects. In lifting-inserting and twisting manipulations, both the left-hand threaded needle and right-hand threaded needle provided more stimulation, but the torsion direction in which they produced better stimulation was the opposite. ConclusionAccording to the simulation results, the ringed pattern enhances stimulation best in the lifting-inserting manipulation, whereas the lined pattern enhances stimulation best in the twisting manipulation. Both the right-hand and left-hand thread patterns have certain enhancing effects in these two operations. Taking the geometric properties of the pattern into account, the left-hand thread pattern and the right-hand thread pattern have the geometric characteristics of both the lined pattern and the ringed pattern. To conclude, a pattern perpendicular to the movement direction during the acupuncture manipulation creates more stimulation. These results have significance for future needle design.Please cite this article as: Sun MZ, Wang X, Li YC, Yao W, Gu W. Mechanical effects of needle texture on acupoint tissue. J Integr Med. 2023; 21(3): 254–267.

Flexible Needle Steering with Tethered and Untethered Actuation: Current States, Targeting Errors, Challenges and Opportunities

Accurate needle targeting is critical for many clinical procedures, such as transcutaneous biopsy or radiofrequency ablation of tumors. However, targeting errors may arise, limiting the widespread adoption of these procedures. Advances in flexible needle (FN) steering are emerging to mitigate these errors. This review summarizes the state-of-the-art developments of FNs and addresses possible targeting errors that can be overcome with steering actuation techniques. FN steering techniques can be classified as passive and active. Passive steering directly results from the needle-tissue interaction forces, whereas active steering requires additional forces to be applied at the needle tip, which enhances needle steerability. Therefore, the corresponding targeting errors of most passive FNs and active FNs are between 1 and 2mm, and less than 1mm, respectively. However, the diameters of active FNs range from 1.42 to 12mm, which is larger than the passive steering needle varying from 0.5 to 1.4mm. Therefore, the development of active FNs is an area of active research. These active FNs can be steered using tethered internal direct actuation or untethered external actuation. Examples of tethered internal direct actuation include tendon-driven, longitudinal segment transmission and concentric tube transmission. Tendon-driven FNs have various structures, and longitudinal segment transmission needles could be adapted to reduce tissue damage. Additionally, concentric tube needles have immediate advantages and clinical applications in natural orifice surgery. Magnetic actuation enables active FN steering with untethered external actuation and facilitates miniaturization. The challenges faced in the fabrication, sensing, and actuation methods of FN are analyzed. Finally, bio-inspired FNs may offer solutions to address the challenges faced in FN active steering mechanisms.

Evaluation of the effect of a resorbable membrane on the closure of palatal fistulas.

A palatal fistula following the closure of palatal clefts remains a difficult clinical complication. Surgical treatment of fistulas is often complicated, with high recurrence rates. We present our results of fistula closure augmented with GTR, a resorbable membrane designed to promote guided tissue regeneration. We reviewed the records of 75 patients operated on between 2008 and 2022 for closure of the palatal fistula. The patients included 24 who underwent fistula closure augmented with GTR and 51 who underwent fistula closure with other techniques. We reviewed the age at surgery, sex, fistula location, and outcome. Operation success was defined as an asymptomatic patient with a healed fistula on clinical examination. The overall fistula closure rate was 79.1% in the GTR group and 76.5% in the non-GTR group(p = 0.79). The success rate of fistula closure in the GTR group is comparable to that in the non-GTR group in this study. An additional advantage is that this procedure does not require harvesting any autologous tissue and reduces tissue damage in the long term.

XBP1 modulates endoplasmic reticulum and mitochondria crosstalk via regulating NLRP3 in renal ischemia/reperfusion injury

The functional status of mitochondria and the endoplasmic reticulum are central to renal ischemia/reperfusion injury (IRI). X-box binding protein 1 (XBP1) is an important transcription factor in endoplasmic reticulum stress. NLR family pyrin domain containing-3 (NLRP3) inflammatory bodies are closely related to renal IRI. In vivo and in vitro, we examined the molecular mechanisms and functions of XBP1-NLRP3 signaling in renal IRI, which influences ER-mitochondrial crosstalk. In this study, mice were subjected to 45 min of unilateral renal warm ischemia, the other kidney resected, and reperfusion was performed for 24 h in vivo. In vitro, murine renal tubular epithelial cells (TCMK-1) were exposed to hypoxia for 24 h and reoxygenation for 2 h. Tissue or cell damage was evaluated by measuring blood urea nitrogen and creatinine levels, histological staining, flow cytometry, terminal deoxynucleotidyl transferase-mediated nick-end labeling, diethylene glycol staining, and transmission electron microscopy (TEM). Western blotting, immunofluorescence staining, and ELISA were used to analyze protein expression. Whether XBP1 regulates the NLRP3 promoter was evaluated using a luciferase reporter assay. Kidney damage was reduced with decreasing blood urea nitrogen, creatinine, interleukin-1β, and interleukin-18 levels. XBP1 deficiency reduced tissue damage and cell apoptosis, protecting the mitochondria. Disruption of XBP1 was associated with reduced NLRP3 and cleaved caspase-1 levels and markedly improved survival. In vitro in TCMK-1 cells, XBP1 interference inhibited caspase-1-dependent mitochondrial damage and reduced the production of mitochondrial reactive oxygen species. The luciferase assay showed that spliced XBP1 isoforms enhanced the activity of the NLRP3 promoter. These findings reveal that XBP1 downregulation suppresses the expression of NLRP3, a potential regulator of endoplasmic reticulum mitochondrial crosstalk in nephritic injury and a potential therapeutic target in XBP1-mediated aseptic nephritis.

Evaluation of the Efficacy of Xyloglucan, Pea Protein and Opuntia ficus-indica Extract in a Preclinical Model of Psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by epidermal gene abnormalities, epidermal barrier defects and inflammation. Corticosteroids are considered to be standard treatments, but often come with side effects and lose efficacy with long-term use. Alternative treatments targeting the epidermal barrier defect are needed to manage the disease. Film-forming substances such as xyloglucan, pea protein and Opuntia ficus-indica extract (XPO) have generated interest for their ability to restore skin barrier integrity and may pose an alternative approach to disease management. Thus, the aim of this two-part study was to evaluate the barrier-protective properties of a topical cream containing XPO on the membrane permeability of keratinocytes exposed to inflammatory conditions and compare its efficacy to dexamethasone (DXM) in an in vivo model of psoriasis-like dermatitis. XPO treatment significantly reduced S. aureus adhesion, subsequent skin invasion and restored epithelial barrier function in keratinocytes. Furthermore, the treatment restored the integrity of keratinocytes, reducing tissue damage. In mice with psoriasis-like dermatitis, XPO significantly reduced erythema, inflammatory markers and epidermal thickening with a superior efficacy to dexamethasone. Given the promising results, XPO may represent a novel steroid-sparing therapeutic for epidermal-related diseases such as psoriasis, thanks to its ability to preserve skin barrier function and integrity.

Antidepressant-like effect of endogenous SO2 on depression caused by chronic unpredictable mild stress.

Sulfur dioxide (SO2) is a toxic gas with harmful effects on various organs. However, recent studies have confirmed the protective effect of SO2 on ischemic heart disease, atherosclerosis, and lung infections. Therefore, the present study was designed to investigate the effect of endogenous SO2 on depression. The chronic unpredictable mild stress (CUMS) model was performed to cause depression. Depression-like behaviors in animals were determined using an open-field test, forced swimming test, and sucrose consumption. Animal spatial learning and memory were also assessed using the Morris water maze. Besides, the oxidative status of the hippocampus and serum corticosterone level were evaluated. A reduction in the tendency to consume sucrose, mobility, and curiosity, as well as learning and memory disorders were observed in CUMS animals. Depressed animals treated with SO2 revealed a significant improvement in behavioral and cognitive functions. SO2 also reduced neuronal damage and lipid peroxidation of the hippocampus and serum corticosterone level in the CUMS group. Various shreds of evidence support a mutual relationship between inflammation and depression; also, growing studies show the role of oxidative stress in the pathogenesis of mood-related disorders such as depression. This study indicated that increased hippocampal malondialdehyde (MDA) and serum corticosterone levels can be due to the existence of oxidative stress and possible activation of inflammatory processes. SO2 donors diminished MDA and corticosterone levels in depressed animals. According to the study results, SO2 may be able to reduce tissue damage and eventually behavioral disorders caused by depression by lowering oxidative stress and inflammation.

Confocal Laser Endomicroscopy for Detection of Early Upper Gastrointestinal Cancer.

Esophageal and gastric cancers are common diseases with high morbidity and mortality; thus, early detection and treatment are beneficial to improve prognosis. Confocal laser endomicroscopy (CLE) is a novel imaging technique that permits the histological analysis of tissues during endoscopy. CLE has been shown to uniquely affect the diagnosis of early upper gastrointestinal cancers. Relevant literature was searched using PubMed and Google Scholar databases. Despite inherent flaws, CLE can reduce tissue damage and improve diagnostic accuracy to a certain extent. CLE in combination with other imaging methods can help enhance the detection rate and avoid unnecessary biopsies in the management of esophageal or gastric cancer and precancerous lesions. CLE is of great significance in the diagnosis and surveillance of early cancers of the upper gastrointestinal tract. Further technical innovations and the standardisation of CLE will make it more responsive to the needs of routine clinical applications.

Macrophages and glia are the dominant P2X7-expressing cell types in the gut nervous system—No evidence for the role of neuronal P2X7 receptors in colitis

The blockade or deletion of the pro-inflammatory P2X7 receptor channel has been shown to reduce tissue damage and symptoms in models of inflammatory bowel disease, and P2X7 receptors on enteric neurons were suggested to mediate neuronal death and associated motility changes. Here, we used P2X7-specific antibodies and nanobodies, as well as a bacterial artificial chromosome transgenic P2X7-EGFP reporter mouse model and P2rx7-/- controls to perform a detailed analysis of cell type-specific P2X7 expression and possible overexpression effects in the enteric nervous system of the distal colon. In contrast to previous studies, we did not detect P2X7 in neurons but found dominant expression in glia and macrophages, which closely interact with the neurons. The overexpression of P2X7 per se did not induce significant pathological effects. Our data indicate that macrophages and/or glia account for P2X7-mediated neuronal damage in inflammatory bowel disease and provide a refined basis for the exploration of P2X7-based therapeutic strategies.

A Ce-MOF@polydopamine composite nanozyme as an efficient scavenger for reactive oxygen species and iron in thalassemia disease therapy.

Patients with β-thalassemia are prone to complications such as cardiovascular diseases and secretory gland injury due to iron overload (IO) and reactive oxygen species (ROS) production caused by blood transfusions. Simultaneously scavenging ROS and eliminating IO using nanomedicine remains challenging. Herein, we designed a dual-functional Ce-based metal-organic framework@polydopamine (Ce-MOF@PDA) composite that integrates oxidative stress reduction and IO elimination and evaluated its protective effect on IO injury in thalassemia. Using Ce-MOF with multiple active sites as the core, dopamine, which can coordinate iron ions, was modified on the surface of Ce-MOF and spontaneously polymerized to obtain PDA with iron elimination ability. Dopamine modification also adjusted the Ce3+/Ce4+ ratio to further enhance the catalytic activity for scavenging ROS. Ce-MOF@PDA exhibited multiple nanozyme activities, such as superoxide dismutase- and catalase-like activities, and decreased iron-mediated oxidative stress levels in vitro. Furthermore, the serum ferritin levels and iron concentrations in the liver of IO mice were reduced following treatment with Ce-MOF@PDA, and the fecal clearance ability was comparable to that of deferoxamine. These results indicate that Ce-MOF@PDA can eliminate IO while scavenging ROS and reduce tissue damage caused by oxidative stress. Therefore, the Ce-MOF@PDA nanozyme is a promising therapeutic nanomedicine for treating thalassemia IO.

Decision to Preserving Ankle Joint Function in Neglected Neck Talus Fracture with Type 2 Diabetic Mellitus Patient : A Case Report

Talus fractures are rare injuries to the hindfoot that still challenging in treatment. The anastomotic ring is likely to be damaged in neck talus fractures, which disrupt the blood flow and cause significant problems affecting fracture healing. Poor fracture healing and an increased risk of surgical complications were also associated with complex diabetes mellitus. We follow the progress of the illness from a 47 year old female complaint pain on her left ankle after falling down 6 months before outpatient. Physical examination shows swelling and varus deformed on affected ankle. Ankle x-ray and CT scan were done. Patient diagnosed as neglected close fracture left neck talus Hawkins type IV with type 2 diabetes mellitus. Then patient undergo an ankle arthroscopy to evaluate ankle joint and preserving ankle joint procedure by subtalar arthrodesis and iliac bone graft. This procedure achieved an excellent result in preserve ankle aligment, stability and soft tissue management. After 2 weeks wound heals without signs of infection and 3 weeks of followup VAS score mention from 0 to 1, with good compliance of the patient. Arthroscopy is safe procedure obtaining anatomical joint surface and reduce tissue damage. While arthrodesis enhance blood supply to encourage bone union, though loss of its ankle motion also has significant effect on ambulation.

Acetazolamide loaded-silver nanoparticles: A potential treatment for murine trichinellosis.

Trichinellosis is a global food-borne disease caused by viviparous parasitic nematodes of the genus Trichinella. Due to the lack of effective, safe therapy and the documented adverse effects of traditional therapy, this study aimed to evaluate the therapeutic effect of acetazolamide-loaded silver nanoparticles (AgNPs) on murine trichinellosis. Fifty male Swiss albino mice were divided into five groups of ten mice each: Group I, normal control group; Group II, infected with T. spiralis and not treated; Group III, infected and given AgNPs; Group IV, infected and treated with acetazolamide; and Group V, infected and treated with acetazolamide-loaded AgNPs. Mice were infected orally with 250 larvae. The efficacy was assessed by counting T. spiralis adults and larvae, measuring serum total antioxidant capacity, and observing the histopathological and ultrastructural alterations. Acetazolamide-loaded AgNPs treatment exhibited the highest percentage of reduction (84.72% and 80.74%) for the intestinal adults and the muscular larvae of T. spiralis-infected animals, respectively. Furthermore, during the intestinal and muscular phases, the serum of the same group had the best free-radical scavenging capacity (antioxidant capacity), which reduced tissue damage induced by oxidative stress. Histopathologically, the normal intestinal and muscular architecture was restored in the group treated with acetazolamide-loaded AgNPs, in addition to the reduced inflammatory infiltrate that alleviated inflammation compared to infected animals. Our results confirmed the marked destruction of the ultrastructural features of T. spiralis adults and larvae. Acetazolamide-loaded AgNPs are a promising therapy against T. spiralis infection.

Recent Updates on Minimally Invasive Spine Surgery: Techniques, Technologies, and Indications.

A number of minimally invasive spine surgeries (MISSs) have been developed to address the drawbacks of open spine surgery. Their advantages include small skin incisions, reduction in tissue damage, quick recovery, and short hospital stay. However, the clinical outcomes are comparable to open surgery. There was a cap on the number of indications that could be set for all spinal illnesses. The indications for MISSs have been expanding owing to mechanical and technological advances in medical equipment. Thus, this review presents the various MISSs developed to date, surgical indications, surgical techniques, and their advantages and disadvantages.

Left Anterior Descending Coronary Artery Ligation for Ischemia-reperfusion Research: Model Improvement via Technical Modifications and Quality Control.

Coronary heart disease is the leading cause of death globally. Complete cessation of blood flow in coronary arteries causes ST-segment elevation myocardial infarction (STEMI), resulting in cardiogenic shock and fatal arrhythmia, which are associated with high mortality. Primary coronary intervention (PCI) for recanalizing the coronary artery significantly improves the outcomes of STEMI, but advancements made in shortening the door-to-balloon time have failed to reduce in-hospital mortality, suggesting that additional therapeutic strategies are required. Left anterior descending coronary artery (LAD) ligation in rats is an animal model for acute myocardial IR research that is comparable to the clinical scenario in which rapid coronary recanalization through PCI is used for STEMI; however, PCI-induced STEMI is a technically challenging and complicated operation associated with high mortality and great variation in infarction size. We identified the ideal position for LAD ligation, created a gadget to control a snare loop, and supported a modified surgical maneuver, thereby reducing tissue damage, to establish a reliable and reproducible acute myocardial ischemia-reperfusion (IR) research protocol for rats. We also propose a method for validating the quality of study results, which is a critical step for determining the accuracy of subsequent biochemical analyses.

Gut microbiota-derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling.

Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota-derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation. AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP. Normobiotic FMT alleviated AP-induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD+ (nicotinamide adenine dinucleotide)-associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP-mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD+ levels. Similarly, overexpression of the NAD+ -dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti-inflammatory activities in AP. Importantly, normobiotic FMT-mediated NMN metabolism induced SIRT3-PRDX5 pathway activation during AP. Gut microbiota-derived NMN alleviates the severity of AP by activating the SIRT3-PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.

Optimizing radiofrequency assisted cryogenic freezing to improve meat microstructure and quality

Radiofrequency-assisted nitrogen cryogenic freezing previously proposed was optimized to increase meat quality. Continuous cryogenic (CCF, for 2.5 min) and pulsed cryogenic (PCF, 3 s pulse with 10 s interval for 10 min) freezing were set up. CCF and PCF were then combined with radiofrequency (RF) pulses to set up RF-CCF (10 s 2 kV RF pulse with 20 s interval during 2.5 min of continuous N 2 flow) and RF-PCF (30 s 2 kV RF pulse with 60 s interval, during 3 s nitrogen pulse with 10 s interval for 10 min). These processes were compared with slow (SF) and blast (BF) freezing. Meat quality ( i.e. , microstructure, drip loss, color, firmness) decreased in the order RF-PCF ≥ PCF > RF-CCF > BF > SF > CCF, indicating that nitrogen pulsing considerably reduced tissue damages and its combination with RF was crucial to further preserve tissue integrity. RF-PCF could be adapted to different matrices by tuning processing conditions. • Radiofrequency (RF) nitrogen cryogenic freezing of meat was optimized by a pulsing approach. • Nitrogen pulsing during meat freezing reduced tissue damage. • RF pulsing was modulated to guarantee homogeneous cryogenic freezing of meat. • Combining nitrogen pulses with RF was crucial to preserve meat microstructure.

The Effect of an Autologous Protein-Based Topical Serum on Cutaneous Burns.

Burns are skin lesions that can be life-threatening. Platelet-rich plasma (PRP) is growing as an effective alternative for the management of burns. The objective of this study was to assess the use of a storable topical serum based on plasma rich in growth factors (PRGF) in promoting burn wound healing, called Endoret-Serum (ES). 3D skin models were used to assess thermal burn injury. Extracellular matrix remodeling, tissue damage, and metabolic activity of explants were analyzed, and a histomorphometric examination was carried out. Silver sulfadiazine cream (SC) was used as control ointment for burn management. Three patients suffering from skin burns were also treated with ES and clinically assessed. Endoret-Serum was based on an enriched platelet fraction with neutral pH and containing a high load of growth factors. Both ES and SC reduced tissue damage after burn, with ES being more effective. ES treatment maintained the metabolic activity of explants at a healthy level, and increased collagen and elastin deposition. Both treatments preserved the cutaneous connective tissue and induced newly synthesized matrix, with ES being more effective. Both treatments induced an intense collagenization, but ES showed better results as it restored the basal layer network with reduced signs of fibrosis. ES decreased the apoptotic cell number. Patients suffering from skin burns showed complete healing after ES treatment. Endoret-Serum might promote cutaneous healing and may be useful for accelerating the regeneration of skin burns. J Drugs Dermatol. 2022;21(12):1330-1339. doi:10.36849/JDD.6763.

Disruption of MenT2 toxin impairs the growth of Mycobacterium tuberculosis in guinea pigs.

Toxin-antitoxin (TA) systems are abundantly present in the genomes of various bacterial pathogens. TA systems have been implicated in either plasmid maintenance or protection against phage infection, stress adaptation or disease pathogenesis. The genome of Mycobacterium tuberculosis encodes for more than 90 TA systems and 4 of these belong to the type IV subfamily (MenAT family). The toxins and antitoxins belonging to type IV TA systems share sequence homology with the AbiEii family of nucleotidyl transferases and the AbiEi family of putative transcriptional regulators, respectively. Here, we have performed experiments to understand the role of MenT2, a toxin from the type IV TA system, in mycobacterial physiology and disease pathogenesis. The ectopic expression of MenT2 using inducible vectors does not inhibit bacterial growth in liquid cultures. Bioinformatic and molecular modelling analysis suggested that the M. tuberculosis genome has an alternative start site upstream of the annotated menT2 gene. The overexpression of the reannotated MenT2 resulted in moderate growth inhibition of Mycobacterium smegmatis. We show that both menT2 and menA2 transcript levels are increased when M. tuberculosis is exposed to nitrosative stress, in vitro. When compared to the survival of the wild-type and the complemented strain, the ΔmenT2 mutant strain of M. tuberculosis was more resistant to being killed by nitrosative stress. However, the survival of both the ΔmenT2 mutant and the wild-type strain was similar in macrophages and when exposed to other stress conditions. Here, we show that MenT2 is required for the establishment of disease in guinea pigs. Gross pathology and histopathology analysis of lung tissues from guinea pigs infected with the ∆menT2 strain revealed significantly reduced tissue damage and inflammation. In summary, these results provide new insights into the role of MenT2 in mycobacterial pathogenesis.

Suppression of innate immunity by the vaccinia virus protein N1 promotes skin microbiota expansion and increased immune infiltration following vaccination.

Vaccinia virus (VACV) protein N1 is an intracellular immunomodulator that contributes to virus virulence via inhibition of NF-κB. Intradermal infection with a VACV lacking gene N1L (vΔN1) results in smaller skin lesions than infection with wild-type virus (WT VACV), but the impact of N1 deletion on the local microbiota as well as the innate and cellular immune responses in infected ear tissue is mostly uncharacterized. Here, we analysed the bacterial burden and host immune response at the site of infection and report that the presence of protein N1 correlated with enhanced expansion of skin microbiota, even before lesion development. Furthermore, early after infection (days 1-3), prior to lesion development, the levels of inflammatory mediators were higher in vΔN1-infected tissue compared to WT VACV infection. In contrast, infiltration of ear tissue with myeloid and lymphoid cells was greater after WT VACV infection and there was significantly greater secondary bacterial infection that correlated with greater lesion size. We conclude that a more robust innate immune response to vΔN1 infection leads to better control of virus replication, less bacterial growth and hence an overall reduction of tissue damage and lesion size. This analysis shows the potent impact of a single viral immunomodulator on the host immune response and the pathophysiology of VACV infection in the skin.

Anti-inflammatory effects of the prostaglandin D2/prostaglandin DP1 receptor and lipocalin-type prostaglandin D2 synthase/prostaglandin D2 pathways in bacteria-induced bovine endometrial tissue

Dairy cows often develop different degrees of endometritis after calving and this is attributed to pathogenic bacterial infections such as by Escherichia coli and Staphylococcus aureus. Infection of the bovine endometrium causes tissue damage and increases the expression of prostaglandin D2 (PGD2), which exerts anti-inflammatory effects on lung inflammation. However, the roles of PGD2 and its DP1 receptor in endometritis in cows remain unclear. Here, we examined the anti-inflammatory roles of the lipocalin-type prostaglandin D2 synthase (L-PGDS)/PGD2 and DP1 receptor regulatory pathways in bovine endometritis. We evaluated the regulatory effects of PGD2 on inflammation and tissue damage in E. coli- and S. aureus-infected bovine endometrial cells cultured in vitro. We found that the secretion of pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and tumour necrosis factor (TNF)-α as well as expression of matrix metalloproteinase (MMP)-2, platelet-activating factor receptor (PAFR), and high mobility group box (HMGB)-1 were suppressed after DP1 receptor agonist treatment. In contrast, IL-6, IL-1β, and TNF-α release and MMP-2, PAFR, and HMGB-1 expression levels were increased after treatment of bovine endometrial tissue with DP1 receptor antagonists. DP1-induced anti-inflammatory effects were dependent on cellular signal transduction. The L-PGDS/PGD2 pathway and DP1 receptor induced anti-inflammatory effects in bovine endometrium infected with S. aureus and E. coli by inhibiting the mitogen-activated protein kinase and nuclear factor-κB signalling pathways, thereby reducing tissue damage. Overall, our findings provide important insights into the pathophysiological roles of PGD2 in bovine endometritis and establish a theoretical basis for applying prostaglandins or non-steroidal anti-inflammatory drugs for treating endometrial inflammatory infertility in bovines.

Molecular docking and molecular dynamics study Lianhua Qingwen granules (LHQW) treats COVID-19 by inhibiting inflammatory response and regulating cell survival.

2019 Coronavirus disease (COVID-19) is endangering health of populations worldwide. Latest research has proved that Lianhua Qingwen granules (LHQW) can reduce tissue damage caused by inflammatory reactions and relieve patients' clinical symptoms. However, the mechanism of LHQW treats COVID-19 is currently lacking. Therefore, we employed computer simulations to investigate the mechanism of LHQW treats COVID-19 by modulating inflammatory response. We employed bioinformatics to screen active ingredients in LHQW and intersection gene targets. PPI, GO and KEGG was used to analyze relationship of intersection gene targets. Molecular dynamics simulations validated the binding stability of active ingredients and target proteins. Binding free energy, radius of gyration and the solvent accessible surface area were analyzed by supercomputer platform. COVID-19 had 4628 gene targets, LHQW had 1409 gene targets, intersection gene targets were 415. Bioinformatics analysis showed that intersection targets were closely related to inflammation and immunomodulatory. Molecular docking suggested that active ingredients (including: licopyranocoumarin, Glycyrol and 3-3-Oxopropanoic acid) in LHQW played a role in treating COVID-19 by acting on CSF2, CXCL8, CCR5, NLRP3, IFNG and TNF. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets. The mechanism of active ingredients in LHQW treats COVID-19 was investigated by computer simulations. We found that active ingredients in LHQW not only reduce cell damage and tissue destruction by inhibiting the inflammatory response through CSF2, CXCL8, CCR5 and IFNG, but also regulate cell survival and growth through NLRP3 and TNF thereby reducing apoptosis.