Hasil untuk "Physiology"

Hiroyuki Sowa, Kohei Karasaki, Mai Ishiwata et al.

Perivascular adipose tissue (PVAT) has emerged as an active paracrine and metabolic organ that modulates vascular function in both humans and rodents, rather than serving merely as structural support. Vascular inflammation is a central mechanism driving cardiovascular diseases such as atherosclerosis, representing a maladaptive response to vascular injury. Recent evidence indicates that PVAT actively participates in this process through dynamic phenotypic changes, including adipose tissue browning or beiging. Furthermore, advances in imaging have enabled the noninvasive evaluation of vascular inflammation using computed tomography–derived indices that reflect PVAT characteristics. This review summarizes current understanding of the interplay between PVAT and vascular inflammation, highlights the biological and clinical implications of PVAT remodeling, and discusses emerging diagnostic approaches and future research directions.

Gana Odeh, Mohammed Alili, Roa Hamshari et al.

Abstract Polycythemia is a hematological condition characterized by an elevated red blood cell (RBC) mass that exceeds the normal range for a specific age and gender; it can be classified as either primary or secondary. This study aimed to estimate the prevalence of primary and secondary polycythemia among adult blood donors in the West Bank and characterize potential risk factors. This cross-sectional study included 674 adult Palestinian male blood donors, aged 18 to 62 years, at An-Najah National University Hospital. Data were collected through face-to-face interviews. Eligible donors underwent complete blood count (CBC) analysis, and samples meeting the latest World Health Organization (WHO) diagnostic criteria for polycythemia, hemoglobin > 16.5 g/dL or hematocrit > 49% in men, were sent for DNA sequencing. Among the participants, 16.6% met the diagnostic criteria for polycythemia; however, none had the JAK2 p.V617F mutation, indicating a potential lack of polycythemia vera (PV). Risk factor analysis revealed an increased risk of polycythemia in moderate (p = 0.039, OR 2.223, [95% CI 1.041–4.746]), heavy cigarette smoking (p = 0.008, OR 2.301, [95% CI 1.246–4.249]), and heavy waterpipe smoking (p ≤ 0.001, OR: 5.019, [95% CI 2.364–10.653]), whereas heavy coffee consumption had a protective effect against polycythemia (p = 0.013, OR 0.444 [95% CI 0.234–0.843]). The absence of the JAK2 p.V617F mutation among participants suggests that secondary polycythemia predominance is driven by smoking and other modifiable lifestyle factors. These findings emphasize the importance of public health efforts focused on lifestyle modification to reduce the risk of polycythemia.

Rodrigo Calderon-Jofre, Giuliano Bernal, Daniel Moraga et al.

Acute and chronic hypoxia modulate the expression of inflammatory mediators known as cytokines. However, studies in chronic and intermittent hypobaric or normobaric hypoxia, like those described in miner’s population, are scarce or absent. In this study, we evaluate the effect of chronic intermittent normobaric hypoxia (CINH) on the hematological response and the expression of lymphocyte cytokines IL-1, IL-2, IL-6, and IL-10 in rats. A total of 20 Sprague-Dawley rats were divided into two groups: a) CINH (FiO2 10%, n = 10) and b) Control (normoxic, n = 10). Systolic arterial pressure and heart rate were measured using a tail-cuff sensor. Blood samples were obtained from both groups for hematological studies, and expression of cytokines obtained from lymphocytes was determined by RT-PCR. Hematocrit, hemoglobin, platelet count, and hematological constant were elevated, and leucocyte count decreased in CINH rats. In addition, systolic arterial pressure in CINH rats was significantly increased (over 50%). Cytokine expression from lymphocytes showed that IL-2, and IL-10 increased by 140% and 38%, respectively; IL-6 showed no significant change, while IL-1β expression decreased by 18%. In this regard, CINH could activate an inflammatory response mediated by IL-2. However, this response could be attenuated by increased IL-10 expression, a known anti-inflammatory cytokine, and decreased IL-1β and IL-6 expression, indicative of an adaptation mechanism to CINH.

Lucrezia Zuccarelli, Maria De Martino, Antonio Filippi et al.

ABSTRACT Background We recently demonstrated that following a 10‐day exposure to inactivity/simulated microgravity impairments of oxidative metabolism were located ‘upstream’ of mitochondrial function, as evaluated by maximal ADP‐stimulated mitochondrial respiration (JO2max) determined ex vivo. The aim of this study was to evaluate mitochondrial sensitivity to submaximal [ADP] by an alternative approach aimed at identifying responses associated with fibre type composition. Methods Isolated permeabilized vastus lateralis fibres were analysed by high‐resolution respirometry in 9 young males before and after a 10‐day horizontal bed rest. Eleven submaximal titrations of ADP (from 12.5 to 10 000 μM) were utilized to assess complex I + II‐linked ADP sensitivity. We applied to JO2 versus [ADP] data a traditional Michaelis–Menten kinetics equation, with the calculation of the apparent Km and maximal respiration (Vmax), and two ‘sequential’ hyperbolic equations, yielding two Km and Vmax values. The two‐hyperbolic equations were solved and the [ADP] value corresponding to 50% of JO2max was calculated. Isoform expression of myosin heavy chains (MyHC) 1, 2A and 2X was also determined. Control experiments were also carried out on rat skeletal muscle samples with different percentages of MyHC isoforms. Results The two hyperbolic equations provided an alternative fitting of data and identified two distinct phases of the JO2 versus [ADP] response: a first phase characterized by low Vmax (Vmax1, 28 ± 10 pmol s−1 mg−1) and apparent Km (Km1, 62 ± 54 μM) and a second phase characterized by higher Vmax (Vmax2, 61 ± 16 pmol s−1 mg−1) and Km (Km2, 1784 ± 833 μM). Data were confirmed in control experiments carried out in rat muscle samples with different percentages of MyHC isoforms. Correlation and receiver operating characteristics analyses suggest that the two phases of the response were related to the % of MyHC isoforms. Conclusions A novel mathematical approach (two sequential hyperbolic functions) for the fitting of JO2 versus [ADP] data obtained by high‐resolution respirometry on permeabilized skeletal muscle fibres, obtained in humans and rats, provided an alternative fitting of the experimental data compared to the traditional Michaelis–Menten kinetics equation. This alternative model allowed the identification of two distinct phases in the responses, which were related to fibre type composition. A first phase, characterized by low apparent Km and Vmax values, was correlated with the percentage of less oxidative (Type 2A + 2X) MyHC isoforms. A second phase, characterized by high apparent Km and Vmax, was related to more oxidative (Type 1) MyHC isoforms.

G. S. Faria, L. Carlos, S. C. Vasconcelos-Filho et al.

Abstract Hymenaea stigonocarpa Mart. ex Hayne has leaves with adaxial and abaxial epidermis covered by a very thick cuticle, in addition to anatomical structures involved in reducing the amount of herbicide absorbed by plants. Thus, we tested the hypothesis that H. stigonocarpa is potentially resistant to the herbicide glyphosate, exposing the plants to different doses (0, 96, 240, 480, and 960 g a.e ha-1). We carried out assessments of the symptoms, anatomy, growth and physiology of the plants and found that exposure to glyphosate negatively affected the height and number of leaves of the plants. Leaf fall resulted in a reduction in the photosynthetic capacity of plants, which responded by investing in stem diameter. Despite this, no visual symptoms of glyphosate toxicity were observed at the concentrations evaluated and histochemical tests did not detect signs of oxidative stress in the leaves, nor starch accumulation, indicating that carbohydrate translocation was not impaired. These results confirm our hypothesis of tolerance of H. stigonocarpa to glyphosate. Furthermore, plants exposed to the lowest doses of glyphosate (96 and 240 g ha-1) showed good growth, photosynthesis, transpiration and photochemical potential responses, indicating a hormetic effect in this application range.

Choriyev Otabek, Dilmurodov Nasriddin, Babanazarov Eshmakhamad et al.

The characteristics of changes in the morphometric dimensions of the skin of horses belonging to the “Karabayir” breed at various physiological stages of postnatal ontogenesis were studied. It was found that the thickness of the skin of various anatomical points of the horse’s body increases rapidly in the 2-3 age stages of postnatal ontogenesis, and in old horses, this indicator decreases, the thickness of the skin of the legs increases in the distal direction in connection with the morphofunctional properties, and the skin elasticity decreases. In connection with the effect of mechanical friction on the skin, it is noted that it is thin in the inner part of the thigh, and the thickest in the soft heel of the hoof, as well as somewhat thick in the lower part of the body of horses, and the thinnest in the ventral part of the head, neck, withers and abdomen. Also, it was found that the dermis of the skin in young horses, the subcutaneous layer (subcutis) thickens in middle-aged horses, and the dermis and subcutaneous layer thins and the skin elasticity decreases in old horses.

Huimeng Yan, Jinyuan Huang, Yingying Li et al.

Abstract Background There is an ongoing debate on whether sex affects immune-suppressive tumor microenvironment and immunotherapy. Here, we explored the underlying molecular bases for sex dimorphisms and their impact on the efficacy of immunotherapy in esophageal cancer (EC). Methods 2360 EC patients from phase 3 trials were pooled to compare overall survivals by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). Genomic data of 1425 samples were integrated to depict the genomic landscapes and antigenic features. We also examined the sex disparities based on single-cell RNA sequencing and T cell receptor-sequencing data from 105,145 immune cells in 60 patients. Results Immunotherapy was associated with favorable outcomes in men (HR, 0.71; 95% CI, 0.65–0.79; P < 0.001), but not in women (HR, 0.98; 95% CI, 0.78–1.23; P = 0.84) (P interaction =0.02). The frequencies of 8 gene mutations, 12 single base substitutions signatures, and 131 reactome pathways were significantly different between male and female. Additionally, six subtypes of HLA-II antigens were enriched in women. Hence, we constructed and then validated a sex-related signature to better predict the outcomes of immunotherapy. Exhausted CD8+ T cells were highly infiltrated in men, while naïve CD8+ T cells were more common in women. Further examinations on multiple malignancies suggested exhausted CD8+ T cells were enriched in patients who responded to immunotherapy. Conclusions Our study delineated the robust genomic and cellular sex disparities in EC. Furthermore, male, rather than female, derived significantly benefits from immunotherapy. These results have implications for treatment decision-making and developing immunotherapy for personalized care. Plain English Summary In the past several years, immunotherapy has gradually replaced the traditional chemotherapy as the standard treatment in esophageal cancer. It is well-established that immunological responses in male and female differ significantly. However, there is an ongoing debate on whether sex can impact the treatment outcomes in immunotherapy. In the present study, we systematically characterized the genomic and cellular landscapes of esophageal cancer, and revealed the significant differences between male and female patients. Furthermore, with over 2000 patients with esophageal cancer, we showed that only men can benefit from immunotherapy. In women, immunotherapy failed to show superior over chemotherapy. These results have implications for treatment decision-making and developing next-generation immunotherapy for personalized care.

Zhao Huibo, Zhao Yong, Luo Rui et al.

The pollution of soil with heavy metals is an increasingly serious worldwide problem, and cadmium (Cd) has attracted attention because of its high toxicity to almost all plants. Since castor tolerates the accumulation of heavy metals, it has the potential for heavy metal soil remediation. We studied the mechanism of the tolerance of castor to Cd stress treatments at three doses: 300 mg/L, 700 mg/L, and 1,000 mg/L. This research provides new ideas for revealing the defense and detoxification mechanisms of Cd-stressed castor. By combining the results of physiology, differential proteomics and comparative metabolomics, we conducted a comprehensive analysis of the networks that regulate the response of castor to Cd stress. The physiological results mainly emphasize the super-sensitive responses of castor plant roots to Cd stress and the effects of Cd stress on plants’ antioxidant system, ATP synthesis and ion homeostasis. We confirmed these results at the protein and metabolite levels. In addition, proteomics and metabolomics indicated that under Cd stress, the expressions of proteins involved in defense and detoxification, energy metabolism and other metabolites such as organic acids and flavonoids were significantly up-regulated. At the same time, proteomics and metabolomics also show that castor plants mainly block the root system’s absorption of Cd2+ by enhancing the strength of the cell wall, and inducing programmed cell death in response to the three different doses of Cd stress. In addition, the plasma membrane ATPase encoding gene (RcHA4), which was significantly upregulated in our differential proteomics and RT-qPCR studies, was transgenically overexpressed in wild type Arabidopsis thaliana for functional verification. The results indicated that this gene plays an important role in improving plant Cd tolerance.

Paula D. Bos, Paula D. Bos, Akihiko Yoshimura et al.

Neda Naghdi, Mohammad Ali Mohseni-Bandpei, Morteza Taghipour et al.

<i>Background and Objective</i>: Previous studies demonstrated that the prevalence of lumbar disc herniation (LDH) is relatively high. This investigation aimed to evaluate the size of lumbar multifidus (LM) muscle in patients with different degrees of LDH compared to healthy group, during rest and contraction, using ultrasonography. <i>Materials and Methods</i>: In this non-experimental, analytic, and case control study, ultrasound imaging was used to assess cross-sectional area (CSA) and thickness of the LM muscle in 15 healthy subjects and 60 patients with different stages of LDH (bulging group = 15, protrusion group = 15, extrusion group = 15, sequestration group = 15). Measurements were taken bilaterally at the L4–L5 level, during rest and contraction and results were compared between groups. <i>Results</i>: There was a significant difference between healthy subjects and the extrusion and sequestration groups during rest and contraction for LM muscle CSA and thickness (<i>p</i> = 0.001), as LM muscle CSA and thickness were significantly smaller in extrusion and sequestration patient groups compared to healthy subjects. LM atrophy was greater in patients with extrusion and sequestration groups than in patients with bulging and protrusion, both at rest and during contraction. Significant correlations were also observed between functional disability and intensity of pain with LM CSA and thickness measurements. <i>Conclusions</i>: Patients with extrusion and sequestration LDH had smaller LM muscle at rest and during contraction compared to healthy subjects. Larger LDH lesions were associated with decreased LM muscle size. Patient with more pain, disability, and extrusion and sequestration LDH had greater LM size changes. LM muscle size was not correlated with symptom duration. Further investigation with greater sample size is warranted.

Yang Chen, Yang Chen, Qiang Wang et al.

There is increasing appreciation for the roles of the gut-liver axis in liver and gall diseases. Specific gut microbes are associated with susceptibility to gallstone diseases, while the relationship between intestinal flora and liver metabolism in the formation of gallstones remains unclear. In this study, an experimental group of model mice was given a lithogenic diet, and a control group was given a normal diet. Both groups were fed for 8 weeks. Integrating 16S rRNA gene sequencing and non-targeted metabolomics to explore the impact of the lithogenic diet on intestinal flora and liver metabolism, Spearman correlation analysis reveals the network of relationships between the intestine and liver. Our findings showed that the gut microbiome and liver metabolome compositions of the test group were significantly changed compared with those of the normal group. Through our research, biomarkers of gallstones were identified at the phylum (5), class (5), order (5), family (7), and genus levels. We predicted the function of the differential flora. We analyzed the liver metabolism of mice with gallstones paired with their flora, and the results showed that there were 138 different metabolites between the two groups. The metabolic pathways enriched by these differential metabolites are highly consistent with the functions of the disordered flora. We focused on an analysis of the relationship between deoxycholic acid, asymmetric dimethylarginine, glucosamine, tauroursodeoxycholic acid, and the disordered flora. This provides a basis for the establishment of the intestine-liver axis in gallstone disease. This research provides a theoretical basis for the research and development of probiotics and prebiotics.

Timofeeva Svetlana Nikolaevna, Kadikov Ilnur Ravilevich, Korchemkin Andrey Aleksandrovich et al.

Due to high athropogenic loads on the environment, issues surrounding public health and safety in consumable products are being raised with ever-increasing frequency. One toxic metal, whose consumption results in irreparable harm to the health of animals and human is cadmium. To antagonize such toxic effects to human health, magnesium and zinc are considered being essential elements and their combination effects warrant further studies. To this end, we developed a Wistar rat model to look at the combinatorial effects of cadmium with magnesium and zinc consumption on the accumulation of iron and zinc ions in kidney and liver tissues. Our findings suggested that exposure to cadmium ions reduced zinc ion levels in the liver and kidneys, reduced iron ions in the liver (but were increased in the kidneys), decreased magnesium ions in the kidneys but increased their levels within the liver. Moreover, while the consumption of magnesium and zinc ions individually, partially reduced the effects caused by cadmium consumption alone, the simultaneous consumption of zinc and magnesium ions proved to be significantly more effective.

H.S. Sunil Gowda, Sajith Purushothaman, K. Ally et al.

The study was carried out to prepare a cost effective straw based densified complete feedblock (DCFB) using dhanwantharam oil residue and tapioca starch waste replacing conventionalbingredients on nutrient basis. Three complete feed blocks T1 (straw based DCFB), T2 (DCFB containing 20 per cent dhanwantharam oil residue) and T3 (DCFB containing 20 per cent tapiocabstarch waste) were formulated according to ICAR (2013) standards. Dry matter content was similar for all the DCFB. Higher crude protein, crude fat and neutral detergent fibre values were recorded in T2 compared to T1 and T3. Higher crude fibre was observed in T3. The cost of production per kgbblock of T1, T2 and T3 were Rs.17.25, 13.89 and 16.42, respectively. Based on the present study, dhanwantharam oil residue and tapioca starch waste can be incorporated in DCFB at 20 per cent inclusion level replacing conventional costly feed ingredients on nutrient basis for the production of low cost DCFB for livestock feeding.

Claudio Costantini, Giorgia Renga, Vasilis Oikonomou et al.

Mast cells are increasingly being recognized as crucial cells in the response of the organism to environmental agents. Interestingly, the ability of mast cells to sense and respond to external cues is modulated by the microenvironment that surrounds mast cells and influences their differentiation. The scenario that is emerging unveils a delicate equilibrium that balances the effector functions of mast cells to guarantee host protection without compromising tissue homeostasis. Among the environmental components able to mold mast cells and fine-tune their effector functions, the microorganisms that colonize the human body, collectively known as microbiome, certainly play a key role. Indeed, microorganisms can regulate not only the survival, recruitment, and maturation of mast cells but also their activity by setting the threshold required for the exploitation of their different effector functions. Herein, we summarize the current knowledge about the mechanisms underlying the ability of the microorganisms to regulate mast cell physiology and discuss potential deviations that result in pathological consequences. We will discuss the pivotal role of the aryl hydrocarbon receptor in sensing the environment and shaping mast cell adaptation at the host-microbe interface.

Dong-Sung Shin, Sung-Hoon Jung, Eun-Young Hong et al.

PURPOSE This study aimed to investigate whether hydrogen (H2) water drinking reduced oxidative damage products (8-hydroxy-2-deoxyguanosine [8-oxo-dG], malondialdehyde [MDA], L-lactate) produced in blood after exercise-induced oxidative stress. METHODS Men (n=7) and women (n=8) (systolic blood pressure [BP]: 90-150 mmHg, diastolic BP: 60-100 mmHg) were recruited. Exercise was performed for 20 minutes (8 km/hr) using treadmill. Placebo or test group drunk water and hydrogen water (1.2-1.5 ppm, 1,000 mL), respectively, right after exercise. Three days after, the same experiment was performed in the cross-over manner. Blood samples were obtained 30 minutes before exercise, right after exercise, and 30, 60, 120 minutes after exercise. 8-oxo-dG, MDA and L-lactate in serum were determined using ELISA kit. RESULTS The blood levels of 8-oxo-dG were significantly increased after exercise (from 381±9.4 to 524±14.9 ng/mL for male; from 367±13.5 to 509±10.7 ng/mL for female). In the placebo group, the increased 8-oxo-dG at each time was not significantly different from the peak level induced by the exercise except that at 120 minutes in female. In the test group, its levels at each time were significantly lower than that in the peak level. The effect of hydrogen water was more pronounced in female than in male. The results obtained with MDA were quite similar to those with 8-oxo-dG. The L-lactate levels were not significant statistically in both groups. CONCLUSIONS The data suggest that the one time drinking of hydrogen water may suppress the exercise-induced oxidative stress.

Sutini Sutini, Susilowati Susilowati, M Rasjad Indra et al.

This study was aimed to assess flavan-3-ol biomass in C. sinensis through callus cultures and suspension cultures derived from leaf explants. Callus initiation of both cultures were using Murashige and Skoog medium were enriched with plant growth regulators Naphtha-lene Acetic Acid 3.0 mg/L and kinetin 2.0 mg/L. The procedures in this study were: (1) callus initiation by cutting the leaves of C. sinen-sis shoots then planted on Murashige and Skoog medium that were enriched with plant growth regulators, (2) sub callus culture on fresh medium that enriched with the same growth regulators, (3) suspension culture initiation of liquid callus, (4) growth examination of callus and suspension cultures in week 12, (5) examination of qualitative-quantitative content of flavan-3-olin suspension cultures at week 4. The results show that suspension cultures contain biomass flavan-3-ol that increase in the same manner of the increase of callus age and weight

Mariana Suárez-Bagnasco

Objetivos: Estudiar la posible asociación entre resiliencia y edad, disfunción ejecutiva y edad, resiliencia y disfunción ejecutiva, en adultos entre 30 y 60 años. Métodos: Estudio piloto, transversal. Participaron 180 sujetos que cumplieron los criterios de inclusión y exclusión. La resiliencia y la disfunción ejecutiva se evaluaron mediante CD-RISC y DEX-sp, respectivamente. Resultados: Ensayando asociaciones bivariadas entre edad, resiliencia y disfunción ejecutiva hallamos asociaciones estadísticamente significativas entre edad y resiliencia (p = 0.001); edad y disfunción ejecutiva (p = 0.001); resiliencia y disfunción ejecutiva (p = 0.001). Conclusiones: Encontramos asociaciones significativas entre edad y resiliencia, edad y disfunción ejecutiva, resiliencia y disfunción ejecutiva, en adultos entre 30 y 60 años. Estudios futuros podrían explorar las variables que median en estas asociaciones y describir las interacciones entre las variables en el tiempo.

Mary Hagedorn, Virginia L Carter

Coral reefs are some of the most diverse and productive ecosystems on the planet, but are threatened by global and local stressors, mandating the need for incorporating ex situ conservation practices. One approach that is highly protective is the development of genome resource banks that preserve the species and its genetic diversity. A critical component of the reef are the endosymbiotic algae, Symbiodinium sp., living within most coral that transfer energy-rich sugars to their hosts. Although Symbiodinium are maintained alive in culture collections around the world, the cryopreservation of these algae to prevent loss and genetic drift is not well-defined. This study examined the quantum yield physiology and freezing protocols that resulted in survival of Symbiodinium at 24 h post-thawing. Only the ultra-rapid procedure called vitrification resulted in success whereas conventional slow freezing protocols did not. We determined that success also depended on using a thin film of agar with embedded Symbiodinium on Cryotops, a process that yielded a post-thaw viability of >50% in extracted and vitrified Symbiodinium from Fungia scutaria, Pocillopora damicornis and Porites compressa. Additionally, there also was a seasonal influence on vitrification success as the best post-thaw survival of F. scutaria occurred in winter and spring compared to summer and fall (P < 0.05). These findings lay the foundation for developing a viable genome resource bank for the world's Symbiodinium that, in turn, will not only protect this critical element of coral functionality but serve as a resource for understanding the complexities of symbiosis, support selective breeding experiments to develop more thermally resilient strains of coral, and provide a 'gold-standard' genomics collection, allowing for full genomic sequencing of unique Symbiodinium strains.

Aditya Jain, Ramta Bansal, KD Singh et al.

Background: Teaching in most Asian countries is still dominated by teacher-centered classrooms in which students passively receive information from the teacher. Studies have shown that students’ inactivity in traditional teacher-centered classes makes them bored that consequently decrease their concentration and learning. To counter these problems active learning methods are being promoted to enhance their interest in studying. This present study was done to explore effective teaching system from a student’s perspective. The aim of the study was to examine the attitude of medical and dental first year students towards teaching methods. Materials and Methods: The study was undertaken at on 150 Medical and Dental first year students. The study was conducted using general questionnaires along with feedback form to know their opinion about different teaching methodology. Results: A 94.67% of the students were unsatisfied with traditional Lecture teaching. 89.33% favoured combination of traditional lectures and active learning techniques, 74.67% students find active learning methods to be interesting, 77.33% found them as attention seekers, 89.33% are motivated for in-depth study and 85.33% students are motivated for independents learning. 100% students agreed that active learning methods provide opportunities of student interaction while 86.67% students are happy with the teacher–student interaction it provides. Audio-visual aids are the most favoured (94.67%) and test questions are most criticized active teaching method. Conclusion: Our study disclosed that the majority of student’s positively believe in using different active learning techniques for classroom activities.

Toru Kanke, Toshiaki Takizawa, Mototsugu Kabeya et al.

PAR-2 is the second member of the family of proteinase-activated receptors activated by trypsin, tryptase, and several other serine proteinases. In order to evaluate the therapeutic potential for PAR-2, we have performed studies on PAR-2-mediated signal transduction and investigated the effects of PAR-2 gene deficiency in disease models. In addition to the G-protein-coupled receptor-mediated common signal transduction pathways, inositol 1,4,5-trisphosphate production and mobilization of Ca2+, PAR-2 can also activate multiple kinase pathways, ERK, p38MAPK, JNK, and IKK, in a cell-type specific manner. The studies using PAR-2-genedeficient mice highlighted critical roles of PAR-2 in progression of skin and joint inflammation. We also describe the development and evaluation of potent and metabolically stable PAR-2 agonists in multiple assay systems both in vitro and in vivo. The structure-activity relationship analysis indicated the improved potencies of furoylated peptides. Furthermore, the resistance of the furoylated peptide against aminopeptidase contributed to the highly potent and sustained effects of the peptide in vivo. These studies suggest the potential therapeutic importance of PAR-2 in inflammatory diseases. Also, the PAR-2-gene-deficient mice and the potent and metabolically stable agonists are shown to be useful tools for evaluating the potency of PAR-2 as a therapeutic target. Keywords:: proteinase-activated receptor (PAR)-2, mitogen-activated peptide kinase, PAR-2-gene-deficient mice, PAR-2-activating peptide