Regulatory effect of sericin protein in inflammatory pathways; A comprehensive review.

Sericin protein is a type of protein derived from silk cocoons. Sericin hydrogen bonds cause adhesion to the silk cocoon. This substance contains a large amount of serine amino acids in its structure. At first, the medicinal properties of this substance were unknown, but today many properties have been discovered for this substance. The unique properties of this substance have made it widely used in the pharmaceutical and cosmetic industries. The applications of Sericin in pharmacy are as follows. Sericin is used to repair wounds by producing collagen. Other uses for the drug include anti-diabetic, anti-cholesterol, metabolic modulator, anti-tumor, heart protection, antioxidant, antibacterial, wound healing, cell proliferation, UV protection, freezing, and skin moisturizing. The physicochemical properties of Sericin have attracted the attention of pharmacists and their widespread use in the production of drugs and treatment of diseases. One of the critical and unique properties of Sericin is its anti-inflammatory property. In this article, this property of Sericin is discussed in detail, and according to the experiments performed by pharmacists, this substance has shown a significant effect in eliminating inflammation. This study aimed to evaluate the impact of Sericin protein in relieving inflammation.

The molecular and clinical significance of the Tie/angiopoietin system in leukemia.

BACKGROUND: Angiogenesis and factors affecting it are one of the most critical elements in vascular proliferation. Although they are essential in generating new vessels, their potential to generate solid tumors is accepted as a pathological condition. Leukemia can be an appropriate example of this condition. AIM: This study aims to evaluate the Tie/angiopoietin system effect in Leukemia. METHODS: Leukemia is a pathological condition in which the uncontrolled proliferation of abnormal cells occurs in the bone marrow or lymphatic system. RESULTS: Based on severity and speed of development, many different types of Leukemia have been discovered through years of studying. Acute lymphocytic Leukemia (ALL), acute myeloid Leukemia (AML), chronic lymphocytic Leukemia (CLL), and chronic myeloid Leukemia (CML) are the four main types of Leukemia. CONCLUSION: Leukemia's function, effects, and medication have been a great concern over the years. Angiogenic factors such as angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), angiopoietin-4 (Ang4), a combination of them and their receptors and their effect on Leukemia are the main purposes discussed in this article.

Metformin improves skin flap survival through nitric oxide system.

BACKGROUND: Metformin has shown cardioprotective effects in experimental models of ischemia reperfusion, which is partially mediated through nitric oxide (NO) synthesis. We investigated the effects of metformin pretreatment in a rat model of random-pattern skin flap, and the probable role of NO system. MATERIALS AND METHODS: In the first experiment, the rats received increasing doses of metformin (150, 200, and 300 mg/kg), 4 h before the procedure. Dorsal skin flaps with caudal pedicles were elevated at the midline and flap survival was measured 7 d after surgery. Pathologic review of the skin flap specimen was performed in a subset of animals. In the second experiment, for evaluation of the role of NO, an NO synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) was administered with and without the effective dose of metformin. In the next experiment, subtherapeutic dose of NO precursor, L-Arginine, was administered with and without subeffective dose of metformin. RESULTS: Metformin pretreatment at doses of 200 and 300 mg/kg significantly increased skin flap survival rate. However, administration of L-NAME abolished the protective effects of metformin. On the other hand, subtherapeutic dose of L-arginine augmented the effects of low-dose metformin and significantly increased skin flap survival. Skin flaps from those rats that received 300 mg/kg metformin pretreatment and those treated with subtherapeutic doses of L-arginine and metformin showed increased vasodilation compared with control group. CONCLUSIONS: Metformin pretreatment can improve skin flap survival through an NO dependent pathway.

Acceleration of skin wound healing with tragacanth (Astragalus) preparation: an experimental pilot study in rats.

Gum tragacanth is a natural complex mixture of polysaccharides and alkaline minerals extracted from species of Astragalus plant, which is found widely in arid regions of the Middle East. In a pilot experimental study we examined the effects of its topical application on wound healing in ten albino adult male rats. Two similar parasagittal elliptical full-thickness wounds (control vs. test samples) were created on the dorsum of each animal. Test group samples were fully covered by a thin layer of gum tragacanth daily. The extent of wound healing was evaluated by planimetric analysis on multiple occasions during the 10-day study period. On the 7th day of the study, the percent of wound closure was significantly higher in gum tragacanth-treated specimens compared to the control samples (87%±2% vs. 70%±4%, P<0.001). The majority of wounds in the test group were completely closed by the 10th day of the study. The difference in wound healing index measured by histological examination on day 10 of the study was also statistically meaningful between the two groups (0.624±0.097 vs. 0.255±0.063, P<0.05). The results of this study clearly showed the useful effects of topical application of gum tragacanth in acceleration of skin wound contraction and healing. More studies are encouraged to identify the implicating agents and precisely understand the mechanism by which they exert their wound healing effects.

Hypothyroidism improves random-pattern skin flap survival in rats.

BACKGROUND: The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps. MATERIALS AND METHODS: Dorsal flaps with caudal pedicles were elevated at midline and flap survival was measured at the seventh day after surgery. The first group, as control, received 1 mL of 0.9% saline solution in the flap before flap elevation. In groups 2 and 3, hypothyroidism was induced by administration of either PTU 0.05% or MMI 0.04% in drinking water. The next four groups received local injections of MMI (10, 20, 50, or 100 µg/flap) before flap elevation. Local PTU injection was ignored due to insolubility of the agent. RESULTS: Hypothyroidism was induced in chronic PTU- and MMI-treated groups, and animals in these groups showed significant increase in their flap survival, compared to control euthyroid rats (79.47% ± 10.49% and 75.48% ± 12.93% versus 52.26% ± 5.75%, respectively, P < 0.01). Acute local treatment of skin flaps with MMI failed to significantly affect the flap survival. CONCLUSION: This study demonstrates for the first time that hypothyroidism improves survival of random-pattern skin flaps in rats.

The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs.

RATIONALE: Studies on the regulation of nerve growth factor (NGF) levels by psychotropics are limited in scope and the mechanism(s) remain elusive which merit further elucidation. OBJECTIVES: We aimed to perform a more comprehensive investigation on the possible effects of pharmacologically heterogeneous groups of psychotropic drugs on NGF contents in the brain regions involved in the modulation of emotions. As a mechanistic approach, we looked at the role of the cannabinergic system which is linked to depression and/or antidepressant effect and appears to interact with neurotrophin signaling. METHODS: Following psychotropic treatment, NGF or endocannabinoid (eCB) contents were quantified by Bio-Rad protein assay and isotope-dilution liquid chromatography/mass spectrometry, respectively. In case of any significant change, the effects of pretreatment with the CB(1) receptor neutral antagonist AM4113 were investigated. RESULTS: Single injection of nortriptyline, isocarboxazid, citalopram, diazepam, risperidone (2.5, 5, and 10 mg/kg, each), and fluphenazine (0.25, 0.5, and 1 mg/kg) into rats did not alter NGF or eCB contents. Following 4-week treatment, all drugs except diazepam elevated NGF or eCB levels in dose-dependent and brain region-specific fashion. Pretreatment with the highest dose of AM4113 (5.6 mg/kg) prevented psychotropic-induced NGF or eCB elevation. AM4113 had no effect by itself. CONCLUSIONS: The cannabinergic system is implicated in the mechanisms of action of certain psychotropic drugs including the upregulation of brain NGF levels. This provides a better understanding of the pathophysiological mechanisms underlying neuropsychiatric disorders, leading to novel drug design.

Chronic lithium impairs skin tolerance to ischemia in random-pattern skin flap of rats.

BACKGROUND: Despite its apparent anti-apoptotic effect, lithium impairs endothelium-dependent vasorelaxation in various tissues. In this study, we assessed the effect of lithium treatment on ischemic skin flap survival and its interaction with nitric oxide pathway. MATERIALS AND METHODS: Seventy-six male Sprague-Dawley rats were randomly assigned into 13 groups. For skin flap surgery, dorsal skin flap measuring 8 × 2 cm was elevated on the midline. After local injections (if needed), the cranial pedicle was cut and flap was sutured back. Flap survival was assessed after 7 d. Animals in the chronic lithium group received lithium chloride in tap water for 4 wk preoperatively and 7 d postoperatively. Acute lithium groups received 3 nmol, 10 nmol and 3 µmol/flap lithium locally. In another experiment, interaction with nitric oxide synthase inhibitor L-NAME as well as nitric oxide precursor L-arginine was studied, and the effect of ischemic preconditioning on skin flap survival in lithium treated rats was investigated. RESULTS: Chronic lithium group had mean flap survival value of 32.6% ± 5.2% (mean ± SD), which was significantly lower than normal subjects (52.7% ± 6.1%, P < 0.001), while acute local lithium treatment had no effect. In chronic lithium group, systemic L-NAME (10 mg/kg, 30 min before flap elevation) failed to significantly decrease the survival, while sub-effective systemic L-arginine (100 mg/kg) and ischemic preconditioning significantly increased flap survival (P < 0.001 and P < 0.01, respectively). CONCLUSIONS: We conclude that long-term lithium treatment impairs the skin tolerance to ischemia in rats, which seems to be nitric oxide mediated. This effect is prevented by ischemic preconditioning or L-arginine treatment. The results suggest that skin-involving interventions should be applied more cautiously in patients who are on lithium treatment.

A computer model for evaluating the osteotomy parameters of Chiari pelvic osteotomy.

This study was conducted to evaluate the effect of the various osteotomy parameters on the biomechanical aspects of the hip joint on a computerised model. The data of the radiographs and a three-dimensional (3D) CT scan of six patients with coverage deficient hip joint were used to construct a 3D computer model. Then Chiari type osteotomies were simulated using various heights, angles and fibrocartilage thicknesses. A new angle called the mid acetabular center edge (MACE) angle was defined in a mid coronal CT cut. The optimum displacement for obtaining the maximum coverage averaged 73%. The angle and height of the osteotomy had a significant effect on the MACE angle (P value < 0.01). Our findings of these Chiari parameters may change the results of the osteotomy. The probability of adapting the proximal osteotomy segment to a deformed femoral head was explained by the model and a modified osteotomy "multiple height osteotomy" was proposed.

Sildenafil decreased cardiac cell apoptosis in diabetic mice: reduction of oxidative stress as a possible mechanism.

Oxidative stress plays a dominant role in the pathogenesis of cardiac cell apoptosis in diabetic patients. Sildenafil has been demonstrated to have antioxidant effects. In this study, the effects of sildenafil on diabetes-induced cardiac cell apoptosis and the antioxidant status of diabetic mouse hearts were investigated. Diabetic mice showed lower body weight gains and heart weights compared with control mice, and sildenafil treatment did not increase these parameters in diabetic mice. Although apoptotic rates, caspase-3 enzyme activity, and malondialdehyde levels were significantly higher in diabetic mouse hearts than in controls, they were reduced in diabetic mice after sildenafil treatment. At the end of the first week, we observed no significant differences in antioxidant enzyme activities (CAT, GSH-Px, and SOD) in diabetic and control groups, whereas at the end of the second week of sildenafil treatment, antioxidant enzyme activities were higher in the diabetic group. In conclusion, our study indicated that sildenafil was beneficial to hearts of diabetic mice by reducing cardiac cell apoptosis, partially because of its antioxidant effects in the heart.

Protective effects of immunophilin ligands on testicular torsion/detorsion damage in rats.

OBJECTIVES: The purpose was to investigate the role of immunophilin ligands in ischemia/reperfusion (I/R)-induced germ cell apoptosis in the rat. MATERIALS AND METHODS: Sprague-Dawley rats were divided into five groups with ten animals in each. In animals undergoing torsion/detorsion, right testes were rotated 720 degrees for 1 h. A baseline group was for basal normal values. The sham-operated group served as a control group. The TD group underwent torsion/detorsion surgery alone; the cyclosporine-A group (TD-CsA) received intravenous cyclosporine injection (5 mg/kg) at the time of detorsion, and the FK-506 group (TD-FK) received intravenous FK-506 (3.5 mg/kg) at the time of detorsion. For measurement of lipid peroxidation and antioxidant enzyme activities, the right testes of five animals in each group were excised after 4-h reperfusion. Germ cell apoptosis indices were determined 24 h following detorsion in the right testes of the remaining five animals in each group. RESULTS: Malondialdehyde (MDA) levels in the TD group were significantly higher compared to control and baseline groups. Moreover, testicular MDA values in TD-CsA and TD-FK groups were significantly lower than in TD. There were also significant decreases in catalase and superxide dismutase activities in the TD group compared to control and baseline groups. These values in TD-CsA and TD-FK groups were significantly higher than in TD. The mean germ cell apoptosis scores were significantly higher in TD animals compared to control and baseline groups; however, CsA and FK-506 treatment significantly reduced the apoptosis compared with the TD group. CONCLUSION: We have shown that administration of immunophilin ligands in testicular torsion decreases ischemia/reperfusion (I/R) cellular damage. The results of biochemical studies suggest that reduction of oxidative stress along with attenuated neutrophil accumulation by immunophilin ligands may have a major role in their cytoprotective effects.

Role of endogenous cannabinoids in ischemia/reperfusion injury following testicular torsion in rats.

OBJECTIVES: The role of endogenous cannabinoids in ischemia/reperfusion induced germ cell apoptosis in rats was investigated. METHODS: Baseline group was for basal normal values. The Sham operated group served as a control group. The torsion/detorsion (T/D) group underwent torsion (1 h) and detorsion; AN1, AN2, and AN3 groups received anandamide (10 mg/kg) 30 min before torsion, 30 min after torsion, and just after detorsion, respectively. In the AM251 group, AM251 (0.5 mg/kg) was injected 45 min before torsion and in the AN/AM group, AM251 and anandamide were injected 45 and 30 min before torsion, respectively. Lipid peroxidation, antioxidant enzymes, and germ cell apoptosis was determined. RESULTS: Malondialdehyde (MDA) levels in the T/D group were significantly higher than the control group. Moreover, MDA values in the AN1, AN2, and AN3 groups were significantly lower than T/D. There were significant decreases in catalase and superoxide dismutase activities in the T/D group versus the control group. These values in the AN1, AN2, and AN3 groups were significantly higher than T/D. It was also shown that MDA levels in the AN/AM group were significantly higher than the AN1 group. In the AN/AM group, catalase and superoxide dismutase activities were significantly lower versus the AN1 group. The mean germ cell apoptosis scores in all animals with testicular T/D were significantly higher than the control group. There was no difference between the apoptotic indices in the AN1, AN2, AN3, and T/D groups. Apoptosis scores in AM251 and AN/AM were significantly higher compared with the T/D and AN1 groups. CONCLUSIONS: Although anandamide increased antioxidant markers, it failed to reduce germ cell apoptosis. AM251 worsened the antioxidant defense system, which is reflected as higher germ cell apoptosis.

Protective effects of sildenafil administration on testicular torsion/detorsion damage in rats.

PURPOSE: We assessed the effectiveness of sildenafil administration during ischemic period in a rat model of testicular torsion/detorsion (T/D). MATERIAL AND METHODS: Sprague-Dawley rats were divided into four groups (n = 10). In those animals that underwent T/D, right testes were rotated 720 degrees for 1 h. Base line group was for basal normal values. Sham operated group was served as a control group. T/D group underwent 1 h testicular torsion. Sildenafil group received sildenafil (0.7 mg/kg) intraperitoneally 30 min after initiation of ischemic period. For measurement of lipid peroxidation and antioxidant enzyme activities, right testes of five animals in each group were excised after 4-h reperfusion. Germ cell apoptosis indices were determined 24 h following detorsion in right testes of remaining five animals in each group. RESULTS: Malondialdehyde (MDA) levels in T/D group were significantly higher versus control and base line groups. Moreover, testicular MDA values in sildenafil group were significantly lower than T/D. There were also significant decreases in catalase and superxide dismutase activities in T/D group compared with control and base line groups. These values were significantly higher in sildenafil group versus T/D. Germ cell apoptosis indices were significantly higher in both groups that experienced T/D in comparison to control and base line groups; however, sildenafil treatment significantly reduced the apoptosis in sildenafil group compared with T/D group. CONCLUSION: Sildenafil administration during testicular torsion decreased ischemia/reperfusion cellular damage. The results of biochemical studies suggest that, reduction of oxidative stress by sildenafil may have a major role in its cytoprotective effects.

Pharmacologic preconditioning of random-pattern skin flap in rats using local cyclosporine and FK-506: interaction with nitric oxide system.

It has been suggested that immunophilin ligands such as cyclosporine and FK-506 (tacrolimus) affect the survival of ischemic tissues. Our objective was to show an acute effect of local cyclosporin-A (CsA) and FK-506 on ischemic protection in a random-pattern skin-flap model in rats and investigate the effect of nitric oxide (NO) pathways as a modulator of protection of these agents. Ninety male Sprague-Dawley rats were randomly assigned to treatment groups. Bipedicled dorsal flaps (2 x 8 cm) were elevated at midline. Prior to cutting the cranial pedicle to induce permanent ischemia, pharmacologic preconditioning groups received local injection of CsA (0.3, 1, or 3 nmol/flap) or FK-506 (0.01, 0.03, or 0.1 pmol/flap), and the ischemic preconditioning (IPC) group underwent temporary clamping of the cranial pedicle. At the seventh day postoperatively, the survival of the flaps was measured. In other groups, nitric oxide synthase inhibitor N omega-nitro-l-arginine methyl ester hydrochloride (L-NAME) was administered with effective CsA and FK-506, and ischemic preconditioning. Nitric oxide precursor L-arginine doses were also studied, and a systemic subeffective dose (100 mg/kg) was coadministered with subeffective CsA and FK-506. Significant increase in flap survival was obtained with CsA (1 nmol/flap), FK-506 (0.1 pmol/flap), and IPC. These protections were abolished by systemic administration of L-NAME (10 mg/kg). Coadministration of subeffective doses of CsA (0.3 nmol/flap) and FK-506 (0.03 pmol/flap), with subeffective systemic l-arginine, significantly improved flap survival.Pharmacologic preconditioning with local, single, low doses of CsA or FK-506 is shown to be even more effective than IPC. Administration of the NOS substrate l-arginine potentiates these effects.

ATP-sensitive potassium channels mediate the anti-ischemic properties of ischemic and pharmacologic preconditioning in rat random-pattern skin flap.

Ischemic preconditioning (IPC) and pharmacologic preconditioning by morphine and adenosine may significantly decrease the amount of necrosis in rat random pattern skin flaps. We examined the role of ATP-sensitive potassium channels (K(ATP) channels) in mediating these protective phenomenon by using glibenclamide a nonspecific blocker of these channels. We also investigated whether administration of diazoxide an opener of the K(ATP) channels could mimic the same protective effect. Ninety male Sprague-Dawley rats were randomly divided into either control or treatment groups (n = 6 each). Bipedicled dorsal skin flaps (2 x 8 cm) were elevated at the midline. In pharmacologic preconditioning groups, 1 mL of morphine (5 mg/flap), adenosine (0.5 mg/flap), or different doses of diazoxide (0.5, 1, 5, and 15 mg/flap) were administered locally in the cranial half of the flap, respectively. One milliliter of saline was locally injected in the control group. In the IPC group, 1 hour after local saline injection the cranial pedicle was clamped for 20 minutes, and then 40 minutes' reperfusion was performed. In another experiment, 0.3 mg/kg of glibenclamide was injected intraperitoneally 30 minutes before local administration of saline or drug in ischemic or pharmacologic preconditioning groups. Regardless of the group, all flaps were cut at the cranial side 2 hours after elevation and were sutured back. Flap survival area was evaluated on the seventh postoperative day. IPC and pharmacologic preconditioning with morphine, adenosine, and diazoxide (in higher doses; 1, 5, and 15 mg/flap) improved survival area compared with the control group. Glibenclamide abolished their protective effect. K(ATP) channels may have a key role in anti-ischemic properties of IPC and pharmacologic preconditioning.