Molecular Mechanisms of Hawthorn Extracts in Multiple Organs Disorders in Underlying of Diabetes: A Review.

Diabetes mellitus (DM) is one of the most important metabolic disorders associated with chronic hyperglycemia and occurs when the body cannot manage insulin secretion, insulin action, or both. Autoimmune destruction of pancreatic beta cells and insulin resistance are the major pathophysiological factors of types 1 and 2 of DM, respectively. Prolonged hyperglycemia leads to multiple organs dysfunctions, including nephropathy, neuropathy, cardiomyopathy, gastropathy, and micro- and macrovascular disorders. The basis of the metabolic abnormalities in carbohydrate, fat, and protein in diabetes is insufficient action of insulin on various target tissues. Medicinal plants are rich sources of bioactive chemical compounds with therapeutic effects. The beneficial effects of leaves, fruits, and flowers extracts of Crataegus oxyacantha, commonly called hawthorn, belonging to the Rosaceae family, are widely used as hawthorn-derived medicines. Data in this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2021. Based on this review, hawthorn extracts appear both therapeutic and protective effects against diabetic-related complications in various organs through molecular mechanisms, such as decreasing triglyceride, cholesterol, very low density lipoprotein and increasing the antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, decreasing malondialdehyde level, and attenuating tumor necrosis factor alpha, interleukin 6 and sirtuin 1/AMP-activated protein kinase (AMPK)/nuclear factor kappa B (NF-κB) pathway and increasing the phosphorylation of glucose transporter 4, insulin receptor substrate 1, AKT and phosphoinositide 3-kinases, and attenuating blood sugar and regulation of insulin secretion, insulin resistance, and improvement of histopathological changes in pancreatic beta cells. Collectively, hawthorn can be considered as one new target for the research and development of innovative drugs for the prevention or treatment of DM and related problems.

Effects of Boiled Dill Seed on Anxiety During Labor: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of boiled dill seed (Anethum graveolens) on anxiety during childbirth compared with oxytocin. METHODS: This study was a randomized clinical trial with 100 pregnant women who were assigned to the oxytocin (50 cases) and the boiled dill seed (50 cases) group by a table of random number. In the boiled dill seed group, 10 g of dill seed was boiled in 100 mL for 10 min and was given to women after filtration once orally at the beginning of active phase. In the oxytocin group, 10 IU of oxytocin in 1000 mL of Ringer solution was prescribed according to the clinical routine. The State-Trait Anxiety Inventory (STAI) in both groups before (at the beginning of the active phase) and after (6 h after the delivery) was completed. Meanwhile, pain intensity and duration of labor, dilatation and effacement scores, Apgar score of newborns, and FHR were measured and evaluated. RESULTS: No statistically significant differences were shown in obvious anxiety scores between the two groups at baseline (P0.05). After the delivery, in the boiled dill seed group, the number of women with severe [0 vs. 8.0% (4/50)] and almost severe [0 vs. 14.0% (7/50)] trait and almost severe [0 vs. 14.0% (7/50)] state anxiety was lower than those in the control group (P=0.050, P=0.041, respectively). Moreover, labor was shorter in the 1st (P 0.01), 2nd (P=0.78) and 3rd (P=0.10) stages in the boiled dill seed group compared to the control group CONCLUSIONS: Dill seed could be used as an effective treatment to reduce anxiety during labor. Dill seed can be effective in reducing the length of labor. Due to lack of maternal and fetal complications, the boiled dill seed could also be used to reduce cesarean section rates in women who are fearful and anxious of delivery. (RCT Code: IRCT201607177065N2).

The Effect of Muscle Graft With Nerve Growth Factor and Laminin on Sciatic Nerve Repair in Rats.

INTRODUCTION: Peripheral nerve injury is one of the most common damages that lead to physical disability. Considering the similarity between the coatings of skeletal muscles and nerve fibers, we conducted this research to determine the effect of muscle graft with Nerve Growth Factor (NGF) and Laminin (L) on nerve repair. METHODS: We cut a 10-mm length of the sciatic nerve from 42 female Wistar rats (Weight: 200±250 g) and equally divided the rats into three groups. In the muscle graft+NGF+laminin group, the degenerated skeletal muscle was sutured with proximal and distal ends of the transected sciatic nerve. Then, NGF (100 ng) and laminin (1.28 mg/mL) were injected into the muscle graft. In the muscle graft group, normal saline was injected into the muscle graft. In the control group, 10 mm of the sciatic nerve was removed without any treatment. Functional recovery was assessed based on Sciatic Functional Index (SFI). Also, tracing motor neurons and histological studies were performed to evaluate nerve repair. The obtained data were analyzed by ANOVA test. RESULTS: The Mean±SD SFI value significantly increased in the muscle graft+NGF+laminin (-76.6±2.9) and muscle graft (-82.1±3.5) groups 60 days after the injury compared to the control group. The Mean±SD number of labeled motor neurons significantly increased in the muscle graft+NGF+laminin (78.6±3.1) and muscle graft (61.3±6.1) groups compared to the control group (P<0.001). The mean number of myelinated axons in the distal segments of the muscle graft+NGF+laminin increased significantly compared to the muscle graft group. CONCLUSION: These findings suggest that muscle graft followed by NGF and laminin administration have therapeutic effects on nerve repair.

Anti-angiogenic effects of CD73-specific siRNA-loaded nanoparticles in breast cancer-bearing mice.

CD73 facilitates tumor growth by upregulation of the adenosine (immunosuppressive factor) in the tumor microenvironment, however, its precise molecular mechanisms is not precisely understood. Regarding the importance of angiogenesis in tumor development and spreading, we decided to assign the anti-angiogenic effects of CD73 suppression. We used chitosan lactate (ChLa) nanoparticles (NPs) to deliver CD73-specific small interfering RNA (siRNA) into cancer cells. Our results showed that treatment of the 4T1 cells with CD73-specific siRNA-loaded NPs led to potent inhibition of cancer cell proliferation and cell cycle arrest, in vitro. This growth arrest was correlated with downregulation of angiogenesis-related molecules including vascular endothelial growth factor (VEGF)-A, VEGF-R2, interleukin (IL)-6, and transforming growth factor (TGF)-ß. Moreover, administration of NPs loaded with CD73-siRNA into 4T1 breast cancer-bearing mice led to tumor regression and increased mice survival time accompanied with downregulation of angiogenesis (VEGF-A, VEGF-R2, VE-Cadherin, and CD31) and lymphangiogenesis (VEGF-C and LYVE-1)-related genes in the tumor site. Furthermore, the expression of angiogenesis promoting factors including IL-6, TGF-ß, signal transducer, and activator of transcription (STAT)3, hypoxia inducible factor (HIF)-1α, and cyclooxygenase (COX)2 was decreased after the CD73 suppression in mice. Moreover, analysis of leukocytes derived from the tumor samples, spleen, and regional lymph nodes showed that they had lower capability for secretion of angiogenesis promoting factors after CD73-silencing. These results indicate that suppression of tumor development by downregulation of CD73 is in part related to angiogenesis arrest. These findings imply a promising strategy for inhibiting tumor growth accompanied with suppressing the angiogenesis process.

Molecular survey of ITS1 spacer and Rickettsia infection in human flea, Pulex irritans.

The human flea is an important ectoparasite causing serious public health problems worldwide. Planning and monitoring the control programs against this vector require the knowledge of population structure and vector competence. This study was carried out to identify molecular structure of internal transcribed spacer 1 (ITS1) of ribosomal gene and its capability in the survey of Pulex irritans populations as well as to investigate Rickettsia infection in these populations. Flea samples were collected via human baits from animal farms in two districts of Zanjan Province, northwest of Iran. The ITS1 region and the partial Rickettsia gltA gene were amplified from the samples of human flea, and 30 amplicons were sequenced. The 1136 collected fleas consisted of 1079 (94.98%) P. irritans, 36 (3.17%) Ctenocephalides canis, and 21 (1.85%) Ctenocephalides felis. Molecular investigation of 182 human fleas detected the infection of Rickettsia sp. in 4.9%. The ITS1 region covered 957 bp and contained three tandem units of 98-99 bp, starting at positions 145, 245, and 331. Multiple alignments of ITS1 sequences showed single-nucleotide polymorphism at position 798, which caused the substitution of cytosine for adenine in the novel haplotype. High frequency of P. irritans and its Rickettsia infection requires the application of vector control measures, and full characterization of Rickettsia sp. and its potential to cause disease in humans. Regarding the consistency of ITS1 region and its ability to differentiate insect communities, further investigations are recommended to identify the role of selective factors in maintenance of this spacer.

Repellency Effect of Essential Oils of some Native Plants and Synthetic Repellents against Human Flea, Pulex irritans (Siphonaptera: Pulicidae).

BACKGROUND: Fleas are important vectors of human and animal disease, and control measures for protection against their bites and flea-borne diseases are necessary. METHODS: The essential oils (EOs) of four native medicinal plants, Ziziphora tenuiore, Myrtus communis, Achillea wilhelmsii and Mentha piperita were isolated by hydrodistillation technique and analyzed by GC-MC. The repellent activity of EOs and synthetic compounds, DEET and permethrin, were assayed on human subjects against field collected fleas. The effective doses of 50% and 90% of EOs and synthetic compounds were estimated by probit analysis of dose and response regression line. RESULTS: Analysis of EOs revealed about 19 major components. All oils were found to be more repellent (ED50 range= 208-955µg cm-2) than DEET and permethrin (ED50 range= 27-182 × 103µg cm-2). Thyme and myrtle oils showed high repellent activities and among the total detected terpenes, thymol (36.26%) and α-pinene (32.5%) were the major components of those oils respectively. CONCLUSION: Low repellent potency of DEET and permethrin against fleas might be related to flea olfactory system and further molecular and electrophysiological studies are required to conceive new ideas for the discovery and development of the next generation of repellents. Based on high repellent activity of thyme and myrtle essential oils against Pulex irritans further studies should be staged to develop their appropriate effective formulations. Likewise, field trials should be carried out to evaluate the operational feasibility and dermal toxicity over a long period.

A Review Study on Phytochemistry and Pharmacology Applications of Juglans Regia Plant.

In recent years, the use of medicinal plants increased considerably; so that today, the use of traditional medicine, as well as medicinal plants is necessary for the aim of producing more effective drugs with fewer side effects and determining the effective doses. With the scientific name of Juglans regia, walnut plant is a medicinal plant with different properties that is considered less, despite having great therapeutic potential in the traditional medicine. The aim of this study was to review the dispersal of walnut plants, the chemical compounds, and therapeutic effects of walnuts on antioxidant activity, antidiabetic, hypolipidemic, antimicrobial, and antihypertensive activities, as well as liver protection. Data of this review study have been collected from the books and scientific articles published in databases such as Science Direct, Web of Science, Scopus, PubMed, and Scientific Information Database. While this plant having high antioxidant capabilities, walnuts are composed of many chemical compounds such as ascorbic acid, flavonoids, quercetin, and caffeic acid. Experimental studies have shown that walnuts reduced blood glucose and lipids and also decreased blood pressure. They have antioxidant, antidiabetic, antimicrobial, and liver-protective properties. The use of walnuts in traditional medicine and review of experimental studies demonstrated the presence of multiple, effective, and useful compounds which may provide the opportunity for the production of lipid-lowering, antidiabetes, and liver protective drugs. Due to the effects of walnuts on improving the complications of various diseases, the need for doing comprehensive clinical trials for the use of walnuts in the treatment of diseases is necessary.

Comparison of repair of peripheral nerve transection in predegenerated muscle with and without a vein graft.

BACKGROUND: Despite substantial research into the topic and valiant surgical efforts, reconstruction of peripheral nerve injury remains a challenging surgery. This study was conducted to evaluate the effectiveness of axonal regeneration of a transected sciatic nerve through a vein conduit containing degenerated skeletal muscle compared with axonal regeneration in a transected sciatic nerve through degenerated skeletal muscle alone. METHODS: In two of the three experimental rat groups, 10 mm of the left sciatic nerve was transected and removed. The proximal and distal ends of the transected sciatic nerve were then approximated and surrounded with either (a) a degenerated skeletal muscle graft; or (b) a graft containing both degenerated skeletal muscle and vein. In the group receiving the combined vein and skeletal muscle graft, the vein walls were subsequently sutured to the proximal and distal nerve stump epineurium. Sciatic functional index (SFI) was used for assessment of functional recovery. Tracing study and histological procedures were used to assess axonal regeneration. RESULTS: At 60 days, the gait functional recovery as well as the mean number of myelinated axons in the middle and distal parts of the sciatic nerve significantly increased in the group with the vein graft compared to rats with only the muscular graft (P < 0.05). Mean diameter of myelinated nerve fiber of the distal sciatic nerve was also improved with the vein graft compared to the muscle graft alone (P < 0.05). The mean number of DiI-labeled motor neurons in the L4-L5 spinal segment increased in the vein with muscle group but was not significantly different between the two groups. CONCLUSIONS: These findings demonstrated that a graft consisting of not only predegenerated muscle, but also predegenerated muscle with vein more effectively supported nerve regeneration, thus promoting functional recovery after sciatic nerve injury in rats.

Age-associated changes on axonal regeneration and functional outcome after spinal cord injury in rats.

This study was conducted to evaluate the association between aging and regenerative potential of spinal cord injury. Three groups of male Sprague-Dawley rats, including young (40 days), mature (5-6 months) and old (28-29 months) were spinally hemisected at the L1 level. The locomotor performance was assessed weekly for eight weeks after lesion using locomotors' rating scale developed by Basso, Bresnahan and Beattie (BBB). In the tracing study, retrograde labeled neuron was counted in the lateral vestibular nucleus for axonal regeneration. From 4-8 weeks, the functional recovery of the young and mature age rats was significantly increased in comparison to the old age group. At 8 weeks, young and mature animals achieved a plateau score of (mean ± SD), 17 ± 1.47 and 16.8 ± 0.70 respectively, and the old rats reached an average score of 13.8±1.63 (P<0.05). The mean number of labeled neurons in the vestibular nucleus in the young group (mean ± SD): 32.05 ± 1.03 increase significantly compared to the older age group 5.01 ± 1.31 (P<0.05). Current findings suggest that axonal repair and functional improvement decrease in aged animals after partial spinal cord injury. Thus, the aging process may affect the regenerative capacity of the injured central nervous system, and axonal regeneration is age dependent.

Highly cadmium tolerant fungi: their tolerance and removal potential.

BACKGROUND: Soil and effluent of lead and zinc industries contain high concentration of cadmium. The present study was conducted to isolate tolerant fungal strains from cadmium -polluted sites in Zanjan province, Iran. METHODS: Cadmium tolerance and bioremediation capacity of seven isolates including Aspergilus versicolor, Aspergillus fumigatus, Paecilomyces sp.9, Paecilomyces sp.G, Terichoderma sp, Microsporum sp,Cladosporium sp were determined. RESULTS: Minimum inhibitory concentration values among 1,000-4,000 mg l-(1)proved great ability of isolated strains to survive in cadmium polluted environments. The most tolerant fungi, Aspergilus versicolor, showed tolerance index of 0.8 in 100 mg l-(1) cadmium agar media. Fungal resistance against cadmium is depended directly on strain's biological function. A. versicolor was found to bioaccumulate over7 mg of cadmium per 1 g of mycelium, followed by 5.878, 5.243, and 5.075, 4.557 by Paecilomyces sp, Aspergilus fumigatus, Microsporum sp and Terichoderma sp, respectively. CONCLUSION: It can be noted that tolerance of the strains appears to be independent from bioaccumulation capacity. Finally, the results indicated that A. versicolor could be a prospective candidate for bioremediation processes.

A new method to calculate the threshold temperature of a perfect blackbody to protect cornea and lens in the range of 780-3,000 nm.

Exposure to IR-A and IR-B radiation, in the wavelength region of 780 nm to 3,000 nm, may lead to the development of cataractogenesis. Estimation of the exposure levels is the first step in controlling adverse health effects. In the present study, the irradiance of a hot blackbody emitter is replaced by its temperature in the exposure limit values for cornea and lens in the range of 780-3,000 nm. This paper explains the development and implementation of a computer code to predict a temperature, defined as Threshold Temperature, which satisfies the exposure limits already proposed by the ICNIRP. To this end, first an infinite series was created for the calculation of spectral radiance by integration with Planck's law. For calculation of irradiance, the initial terms of this infinite series were selected, and integration was performed in the wavelength region of 780 nm to 3,000 nm. Finally, using a computer code, an unknown source temperature that can emit the same irradiance was found. Exposure duration, source area, and observer distance from the hot source were entered as input data in this proposed code. Consequently, it is possible only by measurement of a Planckian emitter temperature and taking into account the distance from source and exposure time for an observer to decide whether the exposure to IR radiation in the range of 780 to 3,000 nm is permissible or not. It seems that the substitution of irradiance by the source temperature is an easier and more convenient way for hygienists to evaluate IR exposures.

Prevalence of vitamin D deficiency and rickets in children with cholestasis in Iran.

This study was aimed to determine prevalence of vitamin D deficiency and rickets in children with cholestatic liver diseases. Forty eight children with established cholestatic liver disease who referred to gastrointestinal clinic of Children Medical Center (Tehran, Iran) between April 2010 and March 2011 were enrolled in a cross-sectional study. Laboratory analysis including calcium, phosphate, albumin, total and direct bilirubin, aminotransferases, alkalinephosphatase (ALP), prothrombin time (PT), parathyroid hormone (PTH), total protein determined by routine laboratory techniques. Mean age of participants was 299.1 ± 676.8 days (range 2-3600 days) whereas twenty one were female (43.8%) and 27 (56.3%) were male. Twenty two (45.8%) had evidences of rickets in X-ray evaluation. Three children with rickets and two with normal X-ray had vitamin D deficiency while ten in rickets group and 16 in normal group had vitamin D insufficiency. The main underlying diseases were anatomical biliary atresia in cases with rickets and idiopathic in other group. Rickets and vitamin D deficiency should be considered in chronic cholestatic children.

The effect of hydro alcoholic extract of Juglans regia leaves in streptozotocin-nicotinamide induced diabetic rats.

Phytotherapy has been achieved to maintain glycemic control in patients with diabetes mellitus. The present study was conducted to evaluate the antihyperglycemic properties of the Juglans regia leaf extract in streptozotocin-nicotinamide induced diabetic rats. Nicotinamide was injected intraperitonealy (i.p.) 15 min before the injection of Streptozotocin (i.p.). One week after induction of diabetes, oral treatment started with extract of Juglans regia and Metformin and continued for 4 weeks. Fasting blood sugar, body weight, serum lipids and insulin level were measured in different groups. A significant reduction of glucose, HbA1c, total cholesterol and serum triglycerides were detected after 4 weeks in rats treated with Juglans regia leaves compared to the control groups. Thus, Juglans regia extract treatment showed potential hypoglycemic and hypolipidemic effects in type 2 diabetic rats.

Evaluating quality of health services in health centres of Zanjan district of Iran.

To assess quality of health services in Zanjan health centres based on clients' expectations and perceptions. The study was conducted by using service quality (SERVQUAL) scale on a sample of 300 females, clients of health care centres in the district of Zanjan, selected by cluster sampling. The results indicated that there were negative quality gaps at five SERVQUAL dimensions. The most and least negative quality gap mean scores were in reliability dimension (-2.1) and tangible (-1.13) respectively. There was statistically significant difference between clients' perceptions and expectations mean scores at all of the five service quality dimensions (P<0.001). The negative quality gap level in health service dimensions can be used as a guideline for redistribution of resources and managerial attempts to reduce quality gaps and improvement of health care quality.

Evaluation of hypoglycemic effect of Morus alba in an animal model.

OBJECTIVE: The objective of the present investigation was to evaluate the therapeutic efficacy of mulberry leaves in an animal model of diabetes. MATERIALS AND METHODS: Animals were treated with mulberry leaf extract 400 mg and 600 mg/kg body weight for 35 days. Blood glucose, glycosylated hemoglobin, triglyceride, LDL, VLDL, HDL, blood urea, cholesterol, number of ß cells, and diameter of the islets of Langerhans were measured at the beginning and at the end of the experiment. RESULTS: Blood glucose level and other parameters (except HDL) were elevated in the diabetic group, but were brought to control group level in the diabetic group treated with 600 mg/kg body weight of mulberry leaf extract. The diameter of the islets and the number of ß cells were reduced in the diabetic group; both parameters were brought to control group level after treatment with mulberry leaf extract. CONCLUSION: Mulberry leaf extract, at a dose of 600 mg/kg body weight, has therapeutic effects in diabetes-induced Wistar rats and can restore the diminished ß cell numbers.