Reduce Tissue Damage Research Articles

Drug exporter expression correlates with group 3 innate lymphoid cell resistance to immunosuppressive agents

Allogeneic hematopoietic cell transplantation (HCT) is often complicated by graft versus host disease (GvHD), an alloreactive immune response triggered by tissue damage. Interleukin (IL)-22 producing type 3 innate lymphoid cells (ILC3) protect epithelial tissues against chemo(radio)therapy-induced damage, suppress alloreactive T cells and mitigate acute GvHD symptoms after allogeneic HCT. Relatively high numbers of ILC before and after allogeneic HCT has been associated with significantly reduced tissue damage and less acute GvHD. While most transplantation conditioning and GvHD prophylaxis regimens are aimed at eliminating host and alloreactive donor lymphocytes, the effect of these regimens on ILC remain elusive. Here, we studied the effect of conditioning chemotherapy and immunosuppressive agents on the survival, proliferation, activation and function of human ILC3 in vitro. Tonsil-derived ILC3 were activated and incubated with agents commonly used to prevent and treat GvHD. While fludarabine, rapamycin, mycophenolic acid and prednisolone suppressed ILC3 to a similar degree as T cells, the effect of other agents, including cyclosporine A, methotrexate, imatinib, ibrutinib and ruxolitinib, was milder on ILC3 than on T cells. ILC3 are less sensitive to immunosuppressants potentially because of their expression of functionally active ATP Binding Cassette Subfamily B Member 1 (ABCB1) drug exporter proteins. This suggests less intracellular accumulation of immunosuppressive agents, which renders ILC3 resistant to these compounds. The present findings may help to develop strategies to simultaneously maintain the tissue protective properties of ILC3 and at the same time suppress alloreactive lymphocytes, which is important in the prevention and treatment of acute GvHD.

Undaria pinnatifida fucoidan contributes to anti-inflammation activity of Bacteroides in fiber-deficient mice via modulation of gut microbiota and protection of intestinal barrier integrity

Bacteroides as potential probiotics has several health benefits to the host, but its practical application faces many challenges due to its inherent properties. In this study, Bacteroides strains isolated from human feces alleviated colonic inflammation in mice, as evidenced by increased colon length and reduced tissue damage. Further study showed that anti-inflammation activity of Bacteroides strains was disturbed by dietary fiber deficiency (FD), which disrupted the balance between gut microbiota and colonic mucus layer, leading to a thinning of colonic mucus layer. A combination of Bacteroides strains and Undaria pinnatifida fucoidan (UPF) better alleviated colonic inflammation than either of them, including increases in the densities of goblet cells and glycoproteins and reduction in intestinal epithelial damage, pro-inflammatory cytokines and oxidative stress. The underlying mechanisms can be attributed to that UPF-induced alterations of mucosal microbiota cannot only directly benefit host health but also create an ecological condition that facilitates Bacteroides strains exert their healthy properties. In addition, both Bacteroides strains and UPF improved FD-induced lipid metabolism abnormality, mainly involving glycerophospholipid metabolism pathway. This study suggests that the application of Bacteroides has certain limitations, and UPF can be developed as a probiotic adjuvant for Bacteroides to enhance human health.

Exosomal miR-127-5p from BMSCs alleviated sepsis-related acute lung injury by inhibiting neutrophil extracellular trap formation

Neutrophil extracellular traps (NETs) play an important role in sepsis-related acute lung injury (ALI). Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and miRNA are becoming promising agents for the treatment of ALI. The current study aimed to elucidate the mechanism by BMSCs-derived exosomes carrying miR-127-5p inhibiting to the formation of NETs in sepsis-related ALI. We successfully isolated exosomes from BMSCs and confirmed that miR-127-5p was enriched in the exosomes. ALI mice treated with BMSCs-derived exosomes histologically improved, and the release of NETs and inflammatory factors in lung tissue and peripheral blood of mice also decreased compared with LPS group, while the protective effect of exosomes was attenuated after the knockdown of miR-127-5p. Using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, we identified CD64 as a direct target of miR-127-5p. Meanwhile, BMSCs-derived exosomes can synergize with anti-CD64 mab in ALI mice to reduce tissue damage, inhibit the release of inflammatory factors and NETs formation. The synergistic effect of exosomes was attenuated when miR-127-5p was down-regulated. These findings suggest that exosomal miR-127-5p derived from BMSCs is a potential therapeutic agent for treatment of sepsis-induced ALI through reducing NETs formation by targeting CD64.

Essential Surgical Techniques During Fully Endoscopic Spine Surgery: A Historical Review and Future Perspectives

Full-endoscopic spine surgery (FESS) offers minimally invasive techniques for treating spinal lesions with smaller incisions, leading to reduced tissue damage and consequently more rapid patient recovery. The essential techniques in FESS —namely, the transforaminal and interlaminar approaches—have evolved with technological advances in endoscopic systems and surgeon expertise. The transforaminal approach consists of “inside-out” and “outside-in” techniques that have distinct applications depending on the patient’s condition. The interlaminar approach, similar to traditional spinal surgery techniques, is gaining wider acceptance due to its efficacy in addressing unique anatomical challenges. Advanced procedures, such as endoscopic laminectomy and interbody fusion surgery, coupled with navigation systems, have broadened the scope of endoscopic spine surgery, making it an increasingly vital tool in modern spinal surgery.

Recovery from Traumatic Brain Injury Is Nociceptin/Orphanin FQ Peptide Receptor Genotype-, Sex-, and Injury Severity-Dependent.

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States, and survivors often experience mental and physical health consequences that reduce quality of life. We previously reported that blockade of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor reduced tissue damage markers produced by blast TBI. The goal of this study was to determine the extent to which N/OFQ and NOP receptor levels change following mild (mTBI) and moderate TBI (modTBI) and whether the absence of the NOP receptor attenuates TBI-induced sequelae. Male and female NOP receptor knockout (KO) or wild-type (WT) rats received craniotomy-only (sham) or craniotomy plus mTBI, or modTBI impact to the left cerebral hemisphere. Neurologic and vestibulomotor deficits and nociceptive hyperalgesia and allodynia found in WT male and female rats following mTBI and modTBI were greatly reduced or absent in NOP receptor KO rats. NOP receptor levels increased in brain tissue from injured males but remained unchanged in females. Neurofilament light chain (NF-L) and glial fibrillary acidic protein (GFAP) expression were reduced in NOP receptor KO rats compared with WT following TBI. Levels of N/OFQ in injured brain tissue correlated with neurobehavioral outcomes and GFAP in WT males, but not with KO male or WT and KO female rats. This study reveals a significant contribution of the N/OFQ-NOP receptor system to TBI-induced deficits and suggests that the NOP receptor should be regarded as a potential therapeutic target for TBI. SIGNIFICANCE STATEMENT: This study revealed that nociceptin/orphanin FQ peptide (NOP) receptor knockout animals experienced fewer traumatic brain injury (TBI)-induced deficits than their wild-type counterparts in a sex- and injury severity-dependent manner, suggesting that NOP receptor antagonists may be a potential therapy for TBI.

Evaluation of lung protection of Sanghuangporus sanghuang through TLR4/NF-κB/MAPK, keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 signaling pathways mediating apoptosis and autophagy

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial pneumonia characterized by chronic and progressive fibrosis with an unknown etiology. Previous pharmacological studies have shown that Sanghuangporus sanghuang possesses various beneficial properties including immunomodulatory, hepatoprotective, antitumor, antidiabetic, anti-inflammatory, and neuroprotective effects. This study used a bleomycin (BLM)-induced IPF mouse model to illustrate the possible benefits of SS in ameliorating IPF. BLM was administered on day 1 to establish a pulmonary fibrosis mouse model, and SS was administered through oral gavage for 21 d. Hematoxylin and eosin (H&E) and Masson’s trichrome staining results showed that SS significantly reduced tissue damage and decreased fibrosis expression. We observed that SS treatment resulted in a substantial lowering in the level of pro-inflammatory cytokines like TGF-β, TNF-α, IL-1β, and IL-6 as well as MPO. In addition, we observed a notable increase in glutathione (GSH) levels. Western blot analysis of SS showed that it reduces inflammatory factors (TWEAK, iNOS, and COX-2), MAPK (JNK, p-ERK, and p-38), fibrosis-related molecules (TGF-β, SMAD3, fibronectin, collagen, α-SMA, MMP2, and MMP9), apoptosis (p53, p21, and Bax), and autophagy (Beclin-1, LC3A/B-I/II, and p62), and notably increases caspase 3, Bcl-2, and antioxidant (Catalase, GPx3, and SOD-1) levels. SS alleviates IPF by regulating the TLR4/NF-κB/MAPK, Keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 pathways. These results suggest that SS has a pharmacological activity that protects the lungs and has the potential to improve pulmonary fibrosis.

SMA-TB: study protocol for the phase 2b randomized double-blind, placebo-controlled trial to estimate the potential efficacy and safety of two repurposed drugs, acetylsalicylic acid and ibuprofen, for use as adjunct therapy added to, and compared with, the standard WHO recommended TB regimen

BackgroundThe duration and regimen of tuberculosis (TB) treatment is currently based predominantly on whether the M. tuberculosis (Mtb) strain is drug-sensitive (DS) or multidrug-resistant (MDR) with doses adjusted by patients’ weight only. The systematic stratification of patients for personalized treatment does not exist for TB. As each TB case is different, individualized treatment regimens should be applied to obtain better outcomes. In this scenario, novel therapeutic approaches are urgently needed to (1) improve outcomes and (2) shorten treatment duration, and host-directed therapies (HDT) might be the best solution. Within HDT, repurposed drugs represent a shortcut in drug development and can be implemented at the short term. As hyperinflammation is associated with worse outcomes, HDT with an anti-inflammatory effect might improve outcomes by reducing tissue damage and thus the risk of permanent sequelae.MethodsSMA-TB is a multicentre randomized, phase IIB, placebo-controlled, three-arm, double-blinded clinical trial (CT) that has been designed in the context of the EC-funded SMA-TB Project (www.smatb.eu) in which we propose to use 2 common non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA) and ibuprofen (Ibu), as an HDT for use as adjunct therapy added to, and compared with, the standard of care (SoC) World Health Organization (WHO)-recommended TB regimen in TB patients. A total of 354 South African and Georgian adults diagnosed with confirmed pulmonary TB will be randomized into SoC TB treatment + placebo, SoC + acetylsalicylic acid or SoC + ibuprofen.DiscussionSMA-TB will provide proof of concept of the HDT as a co-adjuvant treatment and identify the suitability of the intervention for different population groups (different epidemiological settings and drug susceptibility) in the reduction of tissue damage and risk of bad outcomes for TB patients. This regimen potentially will be more effective and targeted: organ saving, reducing tissue damage and thereby decreasing the length of treatment and sequelae, increasing cure rates and pathogen clearance and decreasing transmission rates. It will result in better clinical practice, care management and increased well-being of TB patients.Trial registrationClinicaltrials.gov NCT04575519. Registered on October 5, 2020.

The advantages of a single use retractor for soft tissue protection in direct anterior approach total hip arthroplasty: the preliminary experience.

The anterior hip approach is a procedure with increasing popularity in hip replacement surgery due to its many benefits and the number of surgeons using it is steadily increasing around the world. Less pain, better results in the first few weeks, reduced dislocation rate are the prerogatives of this approach. We analyzed in a group of 26 patients the use of a soft tissue retractor, Alexis Orthopedic Protector, the CPK values in the first third and fifth postoperative day. The results obtained, normalized, demonstrate a slight reduction in tissue damage using the device compared to a control group. In addition to blood values, improved exposure, distribution of leverage, cleanliness of the field and a potential reduction in infectious risk are advantages for the use of an orthopedic surgery retractor. We believe that the adoption of the Alexis Orthopedic Protector provides numerous improvements during the hip arthroplasty surgical procedure, especially when adopting the direct anterior approach, because it distributes the traction forces around the surgical path resulting in greater visibility. However, the small number of patients is not sufficient to perform an accurate statistical analysis and further studies on larger samples will be required.

P-089 effect of testis tissue retrieval on “Micro Mapping Testicular Extraction” (MMTE): comparison with microscopic testicular sperm extraction (Micro TESE) in non-obstructive azoospermia (NOA)

Abstract Study question Is a new sperm retrieval method, Micro Mapping Testicular Extraction (MMTE) comparable to that of Microscopic testicular sperm extraction (Micro TESE)? Summary answer MMTE is comparable to that of Micro TESE regarding sperm retrieval rate (SRR). It can reduce tissue damage and improve intracytoplasmic sperm injection (ICSI) results. What is known already Micro TESE is currently the standard technique for sperm retrieval in NOA. However, the large incision severely damages testicles, complicating repeated Micro TESE, and there is a high risk of testicular atrophy and hypogonadism. New technologies, such as FNA mapping, have also been reported, but these require multiple surgeries, long operation times, and high examination costs. A more accurate and minimally invasive method of sperm retrieval is needed, using a shorter and simpler procedure. Study design, size, duration MMTE requires only a small amount of testicular tissue, obtained through multiple needle holes in the tunica albuginea by micro-squeezing under a microscope. Tissue is divided into four testicular areas: ventral-upper, ventral-lower, dorsal-upper, and dorsal-lower, and samples are immediately searched for sperm. If sperm are found, a small incision is made in the area with good sperm and additional tissue is taken under the microscope. If no sperm are found, routine Micro TESE is performed. Participants/materials, setting, methods From January to November 2022, 25 NOA cases (35.9+/-4.85 years) with indications for Micro TESE were eligible: 15 idiopathic, 6 gr/gr deletion, 2 Klinefelter’s syndrome, 1 b2b4 deletion and 1 other. MMTE was performed on 45 testes: 5 unilateral (Group A) cases and 20 bilateral (Group B) cases. If sperm were found, they were cryopreserved and later used or will be used for ICSI. Main results and the role of chance After MMTE, sperm were found in all 5 cases in Group A. In group B, sperm were found in 6 cases after MMTE. For those sperm positive 11 cases, additional sampling was performed to gain enough sperm for ICSI. Micro TESE was performed for the rest of group B (14 cases, 28 testes), in which no sperm was found by MMTE. Of 2 cases out of 14 cases, only a few sperm were found by Micro TESE. No sperm was found in the rest of 12 cases. As a result, the SRR per patient was 52% (13/25). The weight of tissue sampled was 56.2 mg (15.6-96.2 mg) by MMTE and 224.6mg (206.4-433.2 mg) by Micro TESE, a significant difference. (p < 0.05). To date, ICSI has been performed in the MMTE-positive 11 cases with a partner (33.8+/-3.4 years). In those cases, the fertilization rate was 62.7% (79/126). The blastocyst rate was 31.7% (40/126), and the pregnancy rate per transfer was 75% (6/8). The total testosterone levels before and 1 month after surgery were significantly reduced only in the cases in which no sperm were found by MMTE. Limitations, reasons for caution Two cases that were sperm-positive only by Micro TESE had severe tissue degeneration and tissue was difficult to retrieve from needle holes, so countermeasures were necessary. It is necessary to consider the number of needle holes depending on the size of the testis. The number of cases is still small. Wider implications of the findings MMTE can correct tissue just under the albuginea and can cover areas that are difficult to reach with Micro TESE. The sample can be taken through a small incision, so tissue damage is limited to that of Simple TESE, which improves ICSI results by taking sperm from the best areas. Trial registration number non applicable

Succinate pretreatment attenuates intestinal ischemia-reperfusion injury by inhibiting necroptosis and inflammation via upregulating Klf4

Intestinal ischemia-reperfusion (I/R) injury is a common pathophysiological process in various diseases, and the disruption of the intestinal barrier composed of tight junction proteins is the initiating factor, which then leads to a large number of bacteria and endotoxins in the intestine into the bloodstream causing stress and distant organ damage. The release of inflammatory mediators and abnormal programmed death of intestinal epithelial cells are important factors of intestinal barrier damage. Succinate is an intermediate product of the tricarboxylic acid cycle with anti-inflammatory and pro-angiogenic activities, but its role in the maintenance of intestinal barrier homeostasis after I/R has not been fully elucidated. In this study, we explored the effect of succinate on intestinal ischemia-reperfusion injury and the possible mechanism of its role by flow cytometry, western blotting, real-time quantitative PCR and immunostaining. The results of pretreatment with succinate in the mouse intestinal I/R model and IEC-6 cells hypoxia-reoxygenation (H/R) model revealed a reduction in tissue damage, necroptosis and associated inflammation due to ischemia-reperfusion. Furthermore, it was found that the protective effect of succinate pretreatment may be associated with the transcriptional upregulation of the inflammatory protein KLF4 and the protective effect of intestinal barrier of succinate was diminished after inhibition of KLF4. Thus, our results suggest that succinate can exert a protective effect in intestinal ischemia-reperfusion injury through upregulation of KLF4 and also demonstrate the potential therapeutic value of succinate pretreatment in acute I/R injury of the intestine.

Cod (Gadus) skin collagen peptide powder reduces inflammation, restores mucosal barrier function, and inhibits fibrosis in dextran sodium sulfate-induced colitis in mice

Ethnopharmacological relevanceUlcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Cod (Gadus), a kind of herb from the Chinese herb. Traditionally, it has used to treat trauma, reduce swelling and relieve pain in order to exert its anti-inflammatory activity. Recent reports based on its hydrolyzed or enzymatic extracts have shown its anti-inflammatory, mucosal barrier protecting properties. However, its mechanism of improvement in ulcerative colitis is not clear. Aim of the studyThis study aimed to explore the preventive and protective effect of cod skin collagen peptide powder (CP) on mice with UC and to explore the underlying mechanism. Materials and methodsMice with dextran sodium sulfate (DSS)-induced UC were treated with CP by gavage, and the anti-inflammatory effects of CP were assessed using general physical, pro-inflammatory cytokine, histopathological, immunohistochemical, macrophage flow cytometry, and inflammatory signaling pathway assays. ResultsCP ameliorates inflammation by upregulating mitogen-activated protein kinase phosphatase-1 (MKP-1) and thereby decreasing the phosphorylation levels of P38 and JNK. It also polarizes macrophages in the colon towards the M2 phenotype, which helps to reduce tissue damage and promotes colon repair. At the same time, CP also inhibits the development of fibrosis, one of the complications of UC, by upregulating ZO-1, Occludin, and downregulating α-SMA, Vimentin, Snail, and Slug. ConclusionIn this study, we found CP reduced inflammation in mice with UC by inducing MKP-1 expression, which caused dephosphorylation of mitogen-activated protein kinase (MAPK). CP also restored mucosal barrier function and inhibited the development of fibrosis complicating UC in these mice. Taken together, these results suggested that CP improved the pathological manifestations of UC in mice, suggesting that it can play a biological role as a nutritional supplement for preventing and treating UC.

Decision on Preserving Ankle Joint Function in Neglected Neck Talus Fracture Hawkins Type IV

Introduction: Talus fractures are rare injuries to the hindfoot that still challenging in treatment. Accounting for <1% of foot and ankle fractures, and approximately 50% of them occur at the level of the neck. The anastomotic ring of blood supply is likely to be damaged in neck talus fractures, which disrupt the blood flow and cause significant problems affecting fracture healing and its complication. Case Illustration: We follow the progress of the illness from a 47 years old female complain pain on her left ankle after falling down 6 months before outpatient. Patient diagnosed as neglected close fracture left neck talus Hawkins type IV. Then patient undergo an ankle arthroscopy to evaluate the ankle joint in decision to preserve the tibiotalar joint, while arthrodesis performed in subtalar and talonavicular joints in this patient. This procedure achieved a good result in preserve ankle alignment, stability and soft tissue damage reduction. Improvement of VAS and AOFAS Score from 5 and 39 preoperative to 0 and 81 in follow-up of 3 months after surgery with good compliance of the patient. Discussion: Arthroscopy is safe procedure obtaining anatomical joint surface and reduce tissue damage. Therefore, a clear articular surface must be found during arthroscopy in deciding to preserve the joint function. While subtalar arthrodesis also another option that can enhance blood supply to encourage union, although loss of some ankle motion has significant effect on ambulation.

Targeting TLR4/3 using Chlorogenic acid ameliorates LPS+POLY I:C-induced acute respiratory distress syndrome via alleviating oxidative stress-mediated NLRP3/NF-κB axis.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a life-threatening condition caused due to significant pulmonary and systemic inflammation. Chlorogenic acid (CGA) has been shown to possess potent antioxidant, anti-inflammatory, and immunoprotective properties. However, the protective effect of CGA on viral and bacterial-induced ALI/ARDS is not yet explored. Hence, the current study is aimed to evaluate the preclinical efficacy of CGA in lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (POLY I:C)-induced ALI/ARDS models in vitro and in vivo. Human airway epithelial (BEAS-2B) cells exposed to LPS+POLY I:C significantly elevated oxidative stress and inflammatory signaling. Co-treatment with CGA (10 and 50 µM) prevented inflammation and oxidative stress mediated by TLR4/TLR3 and NLRP3 inflammasome axis. BALB/c mice, when chronically challenged with LPS+POLY I:C showed a significant influx of immune cells, upregulation of pro-inflammatory cytokines, namely: IL-6, IL-1β, and TNF-α, and treatment with intranasal CGA (1 and 5 mg/kg) normalized the elevated levels of immune cell infiltration as well as pro-inflammatory cytokines. D-Dimer, the serum marker for intravascular coagulation, was significantly increased in LPS+ POLY I:C challenged animals which was reduced with CGA treatment. Further, CGA treatment also has a beneficial effect on the lung and heart, as shown by improving lung physiological and cardiac functional parameters accompanied by the elevated antioxidant response and simultaneous reduction in tissue damage caused by LPS+POLY I:C co-infection. In summary, these comprehensive, in vitro and in vivo studies suggest that CGA may be a viable therapeutic option for bacterial and viral-induced ALI-ARDS-like pathology.

Phytochemicals in the treatment of inflammation-associated diseases: the journey from preclinical trials to clinical practice.

Advances in biomedical research have demonstrated that inflammation and its related diseases are the greatest threat to public health. Inflammatory action is the pathological response of the body towards the external stimuli such as infections, environmental factors, and autoimmune conditions to reduce tissue damage and improve patient comfort. However, when detrimental signal-transduction pathways are activated and inflammatory mediators are released over an extended period of time, the inflammatory process continues and a mild but persistent pro-inflammatory state may develop. Numerous degenerative disorders and chronic health issues including arthritis, diabetes, obesity, cancer, and cardiovascular diseases, among others, are associated with the emergence of a low-grade inflammatory state. Though, anti-inflammatory steroidal, as well as non-steroidal drugs, are extensively used against different inflammatory conditions, they show undesirable side effects upon long-term exposure, at times, leading to life-threatening consequences. Thus, drugs targeting chronic inflammation need to be developed to achieve better therapeutic management without or with a fewer side effects. Plants have been well known for their medicinal use for thousands of years due to their pharmacologically active phytochemicals belonging to diverse chemical classes with a number of these demonstrating potent anti-inflammatory activity. Some typical examples include colchicine (alkaloid), escin (triterpenoid saponin), capsaicin (methoxy phenol), bicyclol (lignan), borneol (monoterpene), and quercetin (flavonoid). These phytochemicals often act via regulating molecular mechanisms that synergize the anti-inflammatory pathways such as increased production of anti-inflammatory cytokines or interfere with the inflammatory pathways such as to reduce the production of pro-inflammatory cytokines and other modulators to improve the underlying pathological condition. This review describes the anti-inflammatory properties of a number of biologically active compounds derived from medicinal plants, and their mechanisms of pharmacological intervention to alleviate inflammation-associated diseases. The emphasis is given to information on anti-inflammatory phytochemicals that have been evaluated at the preclinical and clinical levels. Recent trends and gaps in the development of phytochemical-based anti-inflammatory drugs have also been included.

Enhanced cutting performance of electrosurgical units by oil-infused laser-textured surfaces

To enhance the cutting performance of electrosurgical units, urgent demands have been put forward for their work terminal, including an antiadhesion property and less thermal damage. Herein, an oil-infused surface (OIS) was fabricated by nanosecond laser texturing and spin-coating of medical olive oil and then applied to a work terminal (a scalpel). The effects of four laser scanning paths on the morphology of microdimples used for oil storage were investigated. Then, an array of 0° microdimples with vertical wall and symmetry features was selected to create OISs. The fabricated microdimples contained a nanoscale sponge-like morphology, which improved the oil storage capacity. From the point of view of experimental and theoretical analysis, we verified the autonomous sliding behaviour of plasma droplets on the inclined OIS, and the analysis of the viscosities of the oil film and a plasma droplet showed that the sliding velocity of the droplet decreased with increasing microdimple spacing. Cutting experiments proved that the OIS scalpel has excellent antiadhesion properties for multiple biological tissues. In particular, the OIS scalpel can reduce the cutting force by 19.0% and the tissue thermal damage by 30.8% when cutting pork tenderloin compared to the pristine scalpel. During the cutting process, the introduction of an oil film shifts the interfacial separation from within the tissue to the oil film itself, and the film acts as a thermal barrier to reduce tissue damage, thus greatly improving the cutting performance. The present study highlights the practical application of the OIS as an effective tool in the field of electrosurgical units.

A Prospective, Randomized Comparison of the Classical Altemir's Method With the Newer Seldinger's Technique of Submental Intubation.

Submental intubation performed using the classical Altemir's technique is a well-accepted, safe technique for providing optimal operating field to the maxillofacial surgeon, in cases where either nasotracheal or orotracheal intubation is impossible. We propose a new, percutaneous Seldinger's technique of submental intubation as an interesting alternative to the classical Altemir's technique, wherein a percutaneous dilatational tracheostomy kit is used to dilate the submental tract, instead of bluntly dissecting it. We hypothesized that Seldinger's technique would be associated with reduced procedure time and minimal scar formation in patients with maxillofacial fractures. We enrolled 60 patients scheduled to undergo maxillofacial injury fixation under general anesthesia. After consent, the cohort was randomly allocated to undergo submental intubation by either the classical Altemir's technique or Seldinger's technique. As our primary objective, we noted the time taken to complete the procedure of submental intubation. Our secondary objectives were the components of primary outcome, such as disconnection/apnea time, bleeding, and technical difficulties during the procedure. We also observed for complications such as presence of salivary fistula/infection at hospital discharge and scar characteristics at 1- and 3-month follow-up. The median time for performing submental intubation in the Seldinger group was significantly lower than that in the Altemir group (170.5 [136.5-256.0] seconds vs 220.0 [205.5-289.0] seconds; P value, .040). The median disconnection time was also significantly lower in the Seldinger group (12.0 [10.8-20.0] seconds vs 19.0 [15.0-23.0] seconds; P value, .036). Furthermore, significant bleeding was absent in nearly 53.8% of the study participants in the Seldinger group as compared to 25.9% in the Altemir group. At follow-up, there was no evidence of differences in scar characteristics between the 2 groups. Seldinger's technique is associated with shorter procedure time and reduced apnea time due to easier and better tract formation, thus minimizing the effort required to exteriorize the endotracheal tube. Furthermore, as dilation reduces tissue damage, Seldinger's technique is associated with significantly less procedural bleeding. Thus, Seldinger's technique can be safe, easy, and faster to perform compared with the classical Altemir's technique of submental intubation in patients with maxillofacial trauma.

Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

C-Terminal Fibronectin Exerts Beneficial Effects in Reducing Tissue Damage and Modulating Macrophage Function in a Murine Septic Model.

Fibronectin (FN) can improve organ function and slow the progression of sepsis, but full-length FN is hard to be exacted as a therapeutic. This study aimed to investigate the beneficial effects of C-terminal heparin-binding domain polypeptide of FN (rhFNHC-36) in a cecal ligation and puncture (CLP)-mediated murine septic model and explore its regulatory effects on macrophages. Mice were randomly assigned to four groups: unoperated control (Normal), sham operation control (Sham), CLP-operation with intravenous injection of phosphate-buffered saline (CLP+PBS), and CLP-operation with rhFNHC-36 treatment (CLP+rhFNHC-36). Blood and abdominal fluid samples were subjected to bacterial colony formation assays. Organs (liver, spleen, and lung) were undergone histopathological analyses and/or weighed to obtain organ indices. Serum interleukin-6 (IL-6) levels, nitric oxide (NO) release from isolated abdominal macrophages, and chemotactic effect of macrophages were measured with commercial kits. Surface programmed death ligand 1 (PD-L1) expression on macrophages was measured by flow cytometry. Mice in the CLP+PBS group showed a lower survival rate than that in the CLP+rhFNHC-36 group. Improved survival was associated with better clearance of bacterial pathogens, as evidenced by colony formation assays. The CLP-induced decrease in thymus and spleen indices was attenuated by rhFNHC-36 treatments. rhFNHC-36 alleviated sepsis-associated tissue damage in liver, spleen, and lung. CLP-mediated increases in plasma IL-6 levels were reversed by rhFNHC-36 treatment. NO levels in peritoneal macrophages after lipopolysaccharides (LPS)-stimulation in the CLP+rhFNHC-36 group were lower than that in the CLP+PBS group. Notably, macrophages from the CLP+rhFNHC-36 group retained better chemotaxis ability. After LPS challenge, these macrophages had a reduced percentage of PD-L1-positive cells compared to those in the CLP+PBS group. rhFNHC-36 improved survival of mice with CLP-induced sepsis by reducing tissue damage and modulating macrophage function. Our work provides critical insight for developing FN-based and macrophages-targeted therapeutics for treating sepsis.

Acthar Gel Inhibits the Activation of CD4+ and CD8+ T Cells.

Several inflammatory diseases are characterized by elevated T cell counts and high pro-inflammatory cytokine levels. Inhibiting T cell activity may reduce tissue damage associated with these diseases. Acthar® Gel has potent anti-inflammatory properties, yet little is known about its effect on T cells. This study compared the effects of Acthar, synthetic adrenocorticotropic hormone 1-24 (ACTH1-24) depot, and prednisolone in a murine model of T cell activation. Assessments of CD4+ helper and CD8+ cytotoxic T cells and plasma concentrations of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) were made following anti-CD3-activation. Acthar significantly reduced the number of activated CD4+ and CD8+ T cells at amounts comparable to synthetic ACTH1-24 depot or prednisolone. However, Acthar reduced production of IFN-γ, IL-2, and TNF-α significantly more than the other drugs, suggesting that the in vivo immunomodulatory effects of Acthar on T cells are distinct from synthetic ACTH1-24 depot or prednisolone.

Comparison of the effect of Saccharomyces cerevisiae-Megasphaera elsdenii and buffer on growth performance, digestibility, ruminal histomorphometry, and carcass characteristics of fattening lambs in high concentrate diet.

This study aimed to investigate the effect of rumen pH-adjusting additives in the high-concentrated diet on functional traits, nutrient digestion, some meat parameters, and histomorphometry, and rumen histopathology. Twenty-four Arabia male lambs with 3 to 4months old and initial body weight of 23.9 ± 3.15kg were used in a completely randomized design with three treatments and eight replicates. The study was 77days, including 14days of the adaptation period and 63days of the record taking and sampling period. The experimental treatments consisted of a control diet, control diet + sodium bicarbonate buffer, control diet + Megasphaera elsdenii, and Saccharomyces cerevisiae (bacterial-yeast). Rumen fluid was taken by stomach tube at 3h after morning feeding to measure pH. The lambs were weighed every 3weeks during the period, and the body weight changes, average daily gain, and total weight gain were measured, and the feed conversion ratio was calculated. At the end of the experiment, the lambs were slaughtered, and the longissimus dorsi muscle was prepared to determine the meat parameters. For histological studies, the abdominal rumen sac was sampled. There were no differences among treatments in dry matter intake (DMI), daily weight gain (ADG), and feed conversion ratio (P > 0.05). Propionate concentration was higher in the bacteria-yeast treatment than other treatments (P < 0.05). Protein digestibility was higher in control and bacteria-yeast treatments than buffer treatment (P < 0.05). The percentage of meat protein, carcass weight, and dressing percentage in bacterial-yeast treatment was higher than other treatments (P < 0.05). Rumen wall thickness in the buffer and bacterial-yeast receiving treatments was greater than the control treatment and was significant in the buffer treatment compared to the control treatment (P < 0.05). The thickness of rumen epithelial tissue in the buffer and bacterial-yeast recipient treatments was less than the control treatment (P < 0.05). Rumen papillae thickness was higher in the control treatment than other treatments (P < 0.05). Hydropic degeneration and parakeratosis were less in pH-regulating treatments than in control. The results showed that the use of Megasphaera elsdenii could be an effective way to modulate the ruminal fermentation conditions of lambs fed with high concentrate diets. In addition, to increaseing dressing percentage and meat protein, it can also reduce tissue damage and improve ruminal tissue structure.