Reduce Tissue Damage Research Articles

Antarctic Krill Oil Ameliorates Monosodium Iodoacetate-Induced Irregularities in Articular Cartilage and Inflammatory Response in the Rat Models of Osteoarthritis.

The aim of this study was to examine the effects of Antarctic krill oil (FJH-KO) in a rat model of monosodium iodoacetate (MIA) induced osteoarthritis. The effect of FJH-KO on the development and severity of MIA-induced osteoarthritis was assessed using hematoxylin and eosin (H&E) staining and micro-CT. The expression of PGE2, pro-inflammatory cytokines (IL-1β, TNF-α), and arthritics related genes in osteoarthritic rats in response to FJH-KO supplementation was investigated using real time PCR. FJH-KO supplementation in the arthritic rat model reduced tissue damage, cartilage degeneration, and reduced the MIA-induced irregularities in articular cartilage surface. Serum PGE2, IL-1β, IL-6, and TNF-α levels were higher in MIA treated animals, but these levels decreased upon FJH-KO supplementation. When FJH-KO was provided at a dose of 150 mg/kg b.w to MIA-treated animals, it significantly increased the mRNA expression of anabolic factors. The mRNA expression of catabolic factors was significantly decreased MIA-treated animals that were provided FJH-KO at a dose of 100 and 150 mg/kg b.w. Moreover, the mRNA expression of inflammatory mediators was significantly decreased MIA-treated animals supplemented with FJH-KO. These results suggest supplementation with FJH-KO ameliorates the irregularities in articular cartilage surface and improves the inflammatory response in the osteoarthritis. Thus, FJH-KO could serve as a potential therapeutic agent for osteoarthritis treatment.

Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID-19.

ObjectivesCoronavirus disease 2019 (COVID‐19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID‐19. This study is aimed to discover its molecular mechanism and provide potential drug targets.Materials and MethodsAn LQC target and COVID‐19–related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease‐gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein‐protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein.ResultsA gene set of 65 genes was generated. We then constructed a compound‐target network that contained 234 nodes of active compounds and 916 edges of compound‐target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta‐carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID‐19.ConclusionsThe network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection.

Optimizing remote ischemic conditioning (RIC) of cutaneous microcirculation in humans: Number of cycles and duration of acute effects

<h2>Summary</h2><h3>Objective</h3> Non-invasive Remote Ischemic Conditioning (RIC) offers an approach to reduce tissue damage in various organs/tissues. Besides attenuation of Ischemia-Reperfusion injury (I/R), beneficial effects on cutaneous microcirculation of free microsurgical flaps have been reported. Given the recency of this technique, there are considerable gaps in the current understanding of its mechanism of action. As a result, clinical transfer of RIC is prolongated in several fields. We aimed to optimize the RIC protocol by examination of different RIC-cycle numbers and its effect on changes of cutaneous microcirculation and duration. <h3>Methods</h3> 80 subjects were divided into groups (1, 3, 5, 7 RIC cycles). RIC was applied via an inflatable tourniquet. Cutaneous microcirculation was continuously assessed at the contralateral anterior lateral thigh utilizing a ©O2C-device continuously. <h3>Results</h3> RIC caused significant and sustained changes in microcirculation. Four hours after completion of RIC, a maximum increase of +80.8% (CI 1.395–2.221) in blood flow and +23.5% (CI 1.098–1.372) in tissue oxygen saturation was measured (three-cycle group). A higher number of applied cycles was accompanied with significant higher mean pain. <h3>Conclusion</h3> Acute improvement of cutaneous microcirculation due to RIC lasted for at least 4 h after completion of the RIC-protocol. Dose-dependent effects of RIC are likely. With regard to the increase in pain, we recommend a RIC protocol of 3 cycles for future clinical application.

Lentiviral Interleukin-10 Gene Therapy Preserves Fine Motor Circuitry and Function After a Cervical Spinal Cord Injury in Male and Female Mice.

In mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable biomaterial scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, tissue sparing using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons, axons, and muscle innervation at 2weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce tissue damage and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.

Effects of Ischemic Preconditioning and C1 Esterase Inhibitor Administration following Ischemia-Reperfusion Injury in a Rat Skin Flap Model.

Ischemia-reperfusion (I/R) injury is a serious condition that can affect the success rate of microsurgical reconstructions of ischemic amputated limbs and complex tissue defects requiring free tissue transfers. The purpose of this study was to evaluate the effects of ischemic preconditioning (IPC) and C1 esterase inhibitor (C1-Inh) intravenous administration following I/R injury in a rat skin flap model. Superficial caudal epigastric skin flaps (3 cm × 7 cm) were performed on 50 Wistar rats that were randomly divided into five groups. Ischemia was not induced in the control group. All other flaps underwent 8 hours of ischemia prior to revascularization: I/R control group (8-hour ischemia), IPC group (preconditioning protocol + 8-hour ischemia), C1-Inh group (8-hour ischemia + C1-Inh), and IPC + C1-Inh group (preconditioning protocol + 8-hour ischemia + C1-Inh). Survival areas were macroscopically assessed after 1 week of surgery, and histopathological and biochemical evaluations were also measured. There were no significant differences in flap survival between the treatment groups that were suffering 8 hours of ischemia and the control group. A significant increase in neovascularization and lower edema formation were observed in the IPC group compared with that in the I/R group. Biochemical parameters did not show any significant differences. Intravenous administration of C1-Inh did not significantly modulate I/R-related damage in this experimental model, but further research is needed. On the other hand, IPC reduces tissue damage and improves neovascularization, confirming its potential protective effects in skin flaps following I/R injury.

An Improved Power Management System in Electrosurgery Unit Monopolar Design

In using the Electrosurgery unit, improper power settings and modes can cause tissue damage, so it is necessary to adjust the cutting mode and power settings needed. The purpose of this research is to design power control and cutting mode in Electrosurgery using Arduino nano as a regulator of power and pulse or duty cycle. The contribution of this research is the creation of power control and mode in the Electrosurgery unit to increase power and cutting mode. This is to control the electrosurgery power. The LM2907 IC frequency to voltage circuit is used as a voltage regulator, which is issued according to the frequency with the power selection LOW, MEDIUM, HIGH. The method used is the CMOS 4069 device as a frequency generator at 250 kHz, then the driver pulse is passed and controlled by the ATmega328 IC, then forwarded to an inverter circuit that functions to increase the voltage and output in the form of power. After the measurement process is carried out on the inverter input with a Blend mode three value, the voltage value is obtained at the low setting 100 V error 0.03%, medium setting 110V error 0.02%, High setting 120 V Error -0.02%. While the measurement results in the coagulation mode are the low setting error of 100 V 0.05%, the medium setting error is 110V 0.08%. High setting error is 130 V 0.003%. The measurements show that the error in power management is lower than 1%. The results of this study can be implemented in the electrosurgery unit to reduce tissue damage due to a lack of cutting modes and power management.

MicroRNA Expression Profiling of Bone Marrow-Derived Proangiogenic Cells (PACs) in a Mouse Model of Hindlimb Ischemia: Modulation by Classical Cardiovascular Risk Factors.

BackgroundClassical cardiovascular risk factors (CRFs) are associated with impaired angiogenic activities of bone marrow–derived proangiogenic cells (PACs) related to peripheral artery diseases (PADs) and ischemia-induced neovascularization. MicroRNAs (miRs) are key regulators of gene expression, and they are involved in the modulation of PAC function and PAC paracrine activity. However, the effects of CRFs on the modulation of miR expression in PACs are unknown.Aims and MethodsWe used a model of hindlimb ischemia and next-generation sequencing to perform a complete profiling of miRs in PACs isolated from the bone marrow of mice subjected to three models of CRFs: aging, smoking (SMK) and hypercholesterolemia (HC).ResultsApproximately 570 miRs were detected in PACs in the different CRF models. When excluding miRs with a very low expression level (<100 RPM), 40 to 61 miRs were found to be significantly modulated by aging, SMK, or HC. In each CRF condition, we identified downregulated proangiogenic miRs and upregulated antiangiogenic miRs that could contribute to explain PAC dysfunction. Interestingly, several miRs were similarly downregulated (e.g., miR-542-3p, miR-29) or upregulated (e.g., miR-501, miR-92a) in all CRF conditions. In silico approaches including Kyoto Encyclopedia of Genes and Genomes and cluster dendogram analyses identified predictive effects of these miRs on pathways having key roles in the modulation of angiogenesis and PAC function, including vascular endothelial growth factor signaling, extracellular matrix remodeling, PI3K/AKT/MAPK signaling, transforming growth factor beta (TGFb) pathway, p53, and cell cycle progression.ConclusionThis study describes for the first time the effects of CRFs on the modulation of miR profile in PACs related to PAD and ischemia-induced neovascularization. We found that several angiogenesis-modulating miRs are similarly altered in different CRF conditions. Our findings constitute a solid framework for the identification of miRs that could be targeted in PACs in order to improve their angiogenic function and for the future development of novel therapies to improve neovascularization and reduce tissue damage in patients with severe PAD.

Tourniquet fixing prior to knot tying reduces forces during aortic valve replacement: experimental results from 18 surgeons.

To increase the safety of aortic valve replacement, we developed the 'Caput medusae' method, where the prosthesis is prefixed with circumferential tourniquets prior to knot tying. We assumed that an even distribution of forces may help reduce tissue damage. To confirm this theoretically, we compared forces between knots and tourniquets. The experimental set-up included a device with movable acrylic plates, a mounted valve and a set of sutures. Traction forces were measured with a luggage scale. Two different tourniquets were compared individually and as bundles of 15. Force-path curves were generated. Knotting and tourniquet forces of 18 staff surgeons were then compared. Both modalities were measured 10 times on 2 days, resulting in 40 observations per surgeon, or 360 observations per modality. Polyvinyl chloride tourniquets were stiffer than silicone, expressed by a 1.5- to 1.7-fold higher regression-line slope. Fifteen simultaneous tubes produced force increments 7.9-8.9 times higher than their single counterparts. Overall knotting force was 13.64 ± 5.76 vs tourniquet 1.08 ± 0.48 N. Male surgeons' knotting forces were higher compared to female staff (14.76 ± 6.01 vs 10.73 ± 3.74 N; P < 0.001) while tourniquet forces did not differ (1.09 ± 0.47 vs 1.05 ± 0.49 N; P = 0.459). Dedicated valve surgeons (n = 10) tightened the tourniquets more strongly than inexperienced surgeons (1.20 ± 0.52 vs 0.94 ± 0.37 N; P < 0.001); knotting was similar. Multivariable analysis confirmed only valve experience as a predictor of tourniquet strength (experienced surgeons exerted higher force). Tourniquets exert less force on the tissue than knots. When distributed over the circumference, they can reduce local tension and avoid potential paravalvular leakage. Complete or partial use of tourniquets may thus be an additional option to enhance surgical safety.

Optimization of the technique for removal of benign tumors and wound suturing in a general surgical hospital

Aim. To improve the results of surgical treatment in patients with large lipomas by using the device for closing the edges of wounds, allowing local preventive hemostasis in the surgical wound area, to create optimal conditions for atraumatic suturing and thereby reduce the amount of intraoperative bleeding and subsequently reduce the amount of postoperative wound complications.&#x0D; Methods. The results of treatment of 105 patients with different localization of large lipomas were analyzed. Lipomas ranged from 8.0 to 20 cm in diameter. All patients were divided into 2 groups: the control group consisted of 53 (50.5%) patients for which used the traditional technique of tumor excision with closing surgical wounds, and the study group with 52 (49.5%) patients, for which to reduce tissue damage during tumor removal and the edges of wound suturing, one of the device variants developed by us was used, approximation-distraction device. Fisher's exact test was used for the comparison of the outcomes rate, a p-value 0.05 was considered statistically significant.&#x0D; Results. Surgical wound complications occurred in 7 (6.7%) of 105 patients. In the study group, surgical wound complications occurred in 1.9% (1 observation), in the control group 11.3% (6 observations). Surgical wound complications were severity grade I and grade IIIa. Complications of the first grade did not require a debridement and will regress on its own; in grade IIIa complications, an opening, excision and drainage surgical wounds were performed without general anesthesia.&#x0D; Conclusion. Moderate local selective near-tumor tissue compression that occurs when the device branches come closer to each other accelerates spontaneous thrombus formation in damaged small vessels. This creates favorable conditions for the surgeon to work in a dry wound.

Dural Injury in Unilateral Biportal Endoscopic Spinal Surgery.

Study Design:Retrospective study.Objectives:Unilateral biportal endoscopic surgery (UBES) is a popular surgical method used to treat degenerative spinal diseases because of its merits, such as reduced tissue damage and outstanding visual capacity. However, dural injury is the most common complication of UBES with an incidence rate of 1.9% to 5.8%. The purpose of this study was to analyze the pattern of dural injury during UBES and to report the clinical course.Methods:We retrospectively reviewed the medical and radiographic records of surgically treated patients who underwent UBES at a single institute between January 2018 and December 2019.Results:Fifty-three patients, representing 67 segments, underwent UBES. Seven dural injuries occurred, and the incidence rate was 13.2%. Among 16 far lateral approaches, 2 dural injuries of the exiting roots occurred and were treated with fibrin sealant reinforcement. Among 51 median approaches, dural injury occurred at the thecal sac (n = 3) and traversing root (n = 2). A dural injury of the shoulder of the traversing root was treated with a fibrin sealant; however, a defect in the thecal sac required a revision for reconstruction. The other 2 thecal sac injuries were directly repaired via microscopic surgery.Conclusions:Dural injury during UBES can occur because of the various anatomical features of the meningo-vertebral ligaments. Direct repair of the central dural defect should be considered under microscopic vision. A linear tear in the lateral dura or root can be controlled with a simple patchy reinforcement under endoscopic vision.

A Novel Corona Virus (COVID-19) Pandemic, Pathogenesis, Clinical Features and Management Options, Public Health Measures

Introduction: SARS-CoV-2 is an unknown corona virus causing COVID-19 disease responsible for the ongoing pandemic affecting over 190 countries, with a mortality rate of about 5%. The high mortality rate resulted from its ability to elicit cytokine storm via non-specific immune response with delay in specific immune response, notably worst in the elderly, HIV, immunocompromised and cancer diseased patients. The article therefore provides frontline health care workers, the opportunity to understand and equip themselves with management options, public health measures used in coping with COVID-19 infections and enables personnel to make quick preparation for Symptomatic COVID-19 infection in-order to reduce mortalities in health facilities. It also provides a summarised teaching material for medical and allied health students around the world.&#x0D; Methodology: Credible data and information were obtained from the World health organization situation report, Johns Hopkins University Corona Virus resource centre and other notable journal publications. Most information was on public domain.&#x0D; Results: Clinical features reported include pneumonia, renal dysfunction, hepatobiliary dysfunction and residual tissue damage, especially in the lungs in those that survive. The literature highlights the blood work-up picture (Leucopenia, increased cytokines IL-6, ferritin, Serum creatinine, urea, AST, GGT, ALT and Viremia) and radiological features of the disease. ELISA and RT-qPCR test are required for diagnosis using sputum, or pharyngeal swab, blood, serum, urine and faecal samples which lead to faeco-oral transmission. ELISA/RT-PCR is also required for disease exclusions in co-existing epidemics such as MERS-CoV, SARS-COV and other viral diseases. Treatment modalities employed thus far are trials that have produce results including targeted therapy, anti-retroviral, Favipiravir, Remdesivir, antibody-serum and antimalaria drugs such as chloroquine and quinine which are found among some protocols in African setting and other developing countries. Currently, ongoing preventive measures (face mask, social distancing and hand hygiene, community testing, isolation of confirmed cases and tracking of the exposed, remain the key corner-stone in the management of COVID-19 pandemic.&#x0D; Conclusion: COVID -19 disease still remain unclear to many scientists and its pandemic still ongoing. There are many research and clinical trials ongoing while some drugs are used off-label in-order to mitigate the damage caused by the virus in Human body. Cytokine storm needs immunomodulators and viral targeted therapy as discussed in-order to reduce tissue damage, and eventually morbidity and mortalities from COVID-19 infections.

Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID-19 patients.

We propose a new hypothesis that the established drug pentoxifylline deserves attention as a potential repurposed therapeutic for COVID‐19. Pentoxifylline is an immunomodulator with anti‐inflammatory properties. It is a nonselective phosphodiesterase inhibitor and through Adenosine A2A Receptor‐mediated pathways reduces tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferon gamma and may act to reduce tissue damage during the cytokine storm host response to SARS‐CoV‐2 infection. This agent has been used clinically for many years and has a favorable profile of safety and tolerability. Pre‐clinical data support pentoxifylline as effective in cytokine‐driven lung damage. Clinical studies of pentoxifylline in radiation and cytokine‐induced lung damage in humans are positive and consistent with anti‐inflammatory efficacy. Pentoxifylline is a readily available, off‐patent and inexpensive drug, suitable for large‐scale use including in resource‐limited countries. Current trials of therapeutics are largely focused on the inhibition of viral processes. We advocate urgent randomized trials of pentoxifylline for COVID‐19 as a complementary approach to target the host responses.

S1P lyase inhibition protects against sepsis by promoting disease tolerance via the S1P/S1PR3 axis

BackgroundOne-third of all deaths in hospitals are caused by sepsis. Despite its demonstrated prevalence and high case fatality rate, antibiotics remain the only target-oriented treatment option currently available. Starting from results showing that low-dose anthracyclines protect against sepsis in mice, we sought to find new causative treatment options to improve sepsis outcomes.MethodsSepsis was induced in mice, and different treatment options were evaluated regarding cytokine and biomarker expression, lung epithelial cell permeability, autophagy induction, and survival benefit. Results were validated in cell culture experiments and correlated with patient samples.FindingsEffective low-dose epirubicin treatment resulted in substantial downregulation of the sphingosine 1-phosphate (S1P) degrading enzyme S1P lyase (SPL). Consequent accumulation and secretion of S1P in lung parenchyma cells stimulated the S1P-receptor type 3 (S1PR3) and mitogen-activated protein kinases p38 and ERK, reducing tissue damage via increased disease tolerance. The protective effects of SPL inhibition were absent in S1PR3 deficient mice. Sepsis patients showed increased expression of SPL, stable expression of S1PR3, and increased levels of mucin-1 and surfactant protein D as indicators of lung damage.InterpretationOur work highlights a tissue-protective effect of SPL inhibition in sepsis due to activation of the S1P/S1PR3 axis and implies that SPL inhibitors and S1PR3 agonists might be potential therapeutics to protect against sepsis by increasing disease tolerance against infections.FundingThis study was supported by the Center for Sepsis Control and Care (CSCC), the German Research Foundation (DFG), RTG 1715 (to M. H. G. and I. R.) and the National Institutes of Health, Grant R01GM043880 (to S. S.).

Heme oxygenase-1 in protozoan infections: Atale of resistance and disease tolerance.

Heme oxygenase (HO-1) mediates the enzymatic cleavage of heme, a molecule with proinflammatory and prooxidant properties. HO-1 activity deeply impacts host capacity to tolerate infection through reduction of tissue damage or affecting resistance, the ability of the host to control pathogen loads. In this Review, we will discuss the contribution of HO-1 in different and complex protozoan infections, such as malaria, leishmaniasis, Chagas disease, and toxoplasmosis. The complexity of these infections and the pleiotropic effects of HO-1 constitute an interesting area of study and an opportunity for drug development.

Amniotic fluid and breast milk: a rationale for breast milk stem cell therapy in neonatal diseases.

Amniotic fluid and breast milk play important roles in structural development throughout fetal growth and infancy. Given their significance in physical maturation, many studies have investigated the therapeutic and protective roles of amniotic fluid and breast milk in neonatal diseases. Of particular interest to researchers are stem cells found in the two fluids. These stem cells have been investigated due to their ability to self-replicate, differentiate, reduce tissue damage, and their expression of pluripotent markers. While amniotic fluid stem cells have received some attention regarding their ability to treat neonatal diseases, breast milk stem cells have not been investigated to the same extent given the recency of their discovery. The purpose of this review is to compare the functions of amniotic fluid, breast milk, and their stem cells to provide a rationale for the use of breast milk stem cells as a therapy for neonatal diseases. Breast milk stem cells present as an important tool for treating neonatal diseases given their ability to reduce inflammation and tissue damage, as well as their multilineage differentiation potential, easy accessibility, and ability to be used in disease modelling.

Advanced Electrical and Optical Microsystems for Biointerfacing

Electrical and optical biointerfaces have contributed considerably to understanding biological systems. Recent advances in biocompatible materials, structure designs, and fabrication techniques have established flexible and minimally invasive electronic/optoelectronic platforms that laminate onto targeted surface regions or implant into precise locations of biosystems to monitor and control various biological processes at cell, tissue, and organ levels. Herein, recent progress in advanced biointegrated electrical and optical platforms is discussed. An overview of materials and device designs to form flexible and even stretchable electrodes is presented. Strategies to reduce tissue damage and foreign‐body response to improve chronic stability are described. State‐of‐the‐art wearable and implantable microsystems with/without wireless capabilities for bioelectrical sensing and stimulation, optical recording and modulation, and multimodal operation are highlighted. In conclusion, a discussion of the remaining obstacles for future research in these areas is provided.

Multiple doses of umbilical cord blood cells improve long-term brain injury in the neonatal rat

BackgroundHypoxic ischemic (HI) insults during pregnancy and birth can result in neurodevelopmental disorders, such as cerebral palsy. We have previously shown that a single dose of umbilical cord blood (UCB) cells is effective at reducing short-term neuroinflammation and improves short and long-term behavioural outcomes in rat pups. A single dose of UCB was not able to modulate long-term neuroinflammation or brain tissue loss. In this study we examined whether multiple doses of UCB can modulate neuroinflammation, decrease cerebral tissue damage and improve behavioural outcomes when followed up long-term. MethodsHI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received either 1 dose (PND11), or 3 doses (PND11, 13, 20) of UCB cells. Rats were followed with behavioural testing, to assess both motor and cognitive outcomes. On PND50, brains were collected for analysis. ResultsHI brain injury in rat pups caused significant behavioural deficits. These deficits were significantly improved by multiple doses of UCB. HI injury resulted in a significant decrease in brain weight and left hemisphere tissue, which was improved by multiple doses of UCB. HI resulted in increased cerebral apoptosis, loss of neurons and upregulation of activated microglia. Multiple doses of UCB modulated these neuropathologies. A single dose of UCB at PND11 did not improve behavioural or neuropathological outcomes. ConclusionsTreatment with repeated doses of UCB is more effective than a single dose for reducing tissue damage, improving brain pathology and restoring behavioural deficits following perinatal brain injury.

Hyaluronidase: An overview of its properties, applications, and side effects.

Hyaluronidase, an enzyme that breaks down hyaluronic acid, has long been used to increase the absorption of drugs into tissue and to reduce tissue damage in cases of extravasation of a drug. With the increasing popularity of hyaluronic acid filler, hyaluronidase has become an essential drug for the correction of complications and unsatisfactory results after filler injection. For this reason, when performing procedures using hyaluronic acid filler, a sufficient knowledge of hyaluronidase is required. In order for hyaluronidase to dissolve a hyaluronic acid filler, it must interact with its binding sites within the hyaluronic acid. The reaction of a filler to hyaluronidase depends on the hyaluronic acid concentration, the number of crosslinks, and the form of the filler. Hyaluronidase is rapidly degraded and deactivated in the body. Therefore, in order to dissolve a hyaluronic acid filler, a sufficient amount of hyaluronidase must be injected close to the filler. If the filler is placed subcutaneously, injection of hyaluronidase into the filler itself may help, but if the filler is placed within a blood vessel, it is sufficient to inject hyaluronidase in the vicinity of the vessel, instead of into the filler itself. Allergic reactions are a common side effect of hyaluronidase. Most allergic reactions to hyaluronidase are local, but systemic reactions may occur in infrequent cases. Since most allergic responses to hyaluronidase are immediate hypersensitivity reactions, skin tests are recommended before use. However, some patients experience delayed allergic reactions, which skin tests may not predict.

Hepatoprotective activity of the ethanol extract of Curcuma heyneana rhizome on isoniazid and rifampin-induced liver injury rats

Introduction: Isoniazid (INH) and rifampin (RIF) are antituberculosis drugs that can induce injury in the liver. The purpose of this study was to investigate the antioxidant and hepatoprotective activities of the ethanol extract of Curcuma heyneana rhizome on liver injury in animal model induced by INH and RIF. Methods: Antioxidant activity was measured by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. All animals were divided into 7 groups. Liver injury was induced by using combination of INH at the dose of 50 mg/kg and RIF at the dose of 100 mg/kg. These drugs were administrated for 15 days along with extracts at doses of 5, 25, 125 or 625 mg/kg. Positive control group was given catechin. On the 16th day, the rats were sacrificed, blood and livers were collected for assessment of biochemical parameters like alanine transaminase (ALT) and aspartate transaminase (AST) and histological studies, respectively. Results: The ethanol extract strongly scavenged DPPH with inhibition concentration 50 (IC50) of 82.48 ppm. Administration of ethanol extract of C. heyneana rhizome at the dose of 25, 125 or 625 mg/kg significantly inhibited the elevation of AST and ALT (P&lt;0.01). Moreover, the effects caused by administration of the extracts were similar to the effects caused by catechins. Various doses of the extract could effectively reduce tissue damage. Conclusion: This result suggests that ethanol extract of C. heyneana rhizome at the doses of 25, 125 and 625 mg/kg might be effective as hepatoprotective agent.

Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure.

The main role of the human immune system is to eliminate cells presenting foreign antigens and abnormal patterns, while maintaining self-tolerance. However, when facing highly variable pathogens or antigens very similar to self-antigens, this system can fail in completely eliminating the anomalies, leading to the establishment of chronic pathologies. Prototypical examples of immune system defeat are cancer and Human Immunodeficiency Virus-1 (HIV-1) infection. In both conditions, the immune system is persistently exposed to antigens leading to systemic inflammation, lack of generation of long-term memory and exhaustion of effector cells. This triggers a negative feedback loop where effector cells are unable to resolve the pathology and cannot be replaced due to the lack of a pool of undifferentiated, self-renewing memory T cells. In addition, in an attempt to reduce tissue damage due to chronic inflammation, antigen presenting cells and myeloid components of the immune system activate systemic regulatory and tolerogenic programs. Beside these homologies shared between cancer and HIV-1 infection, the immune system can be shaped differently depending on the type and distribution of the eliciting antigens with ultimate consequences at the phenotypic and functional level of immune exhaustion. T cell differentiation, functionality, cytotoxic potential and proliferation reserve, immune-cell polarization, upregulation of negative regulators (immune checkpoint molecules) are indeed directly linked to the quantitative and qualitative differences in priming and recalling conditions. Better understanding of distinct mechanisms and functional consequences underlying disease-specific immune cell dysfunction will contribute to further improve and personalize immunotherapy. In the present review, we describe relevant players of immune cell exhaustion in cancer and HIV-1 infection, and enumerate the best-defined hallmarks of T cell dysfunction. Moreover, we highlight shared and divergent aspects of T cell exhaustion and T cell activation to the best of current knowledge.