Suppression of Inflammatory and Fibrotic Signals by Cinnamon (Cinnamomum cassia) and Cinnamaldehyde in Cyclophosphamide-Induced Overactive Bladder in Mice

Cinnamon (Cinnamomum cassia) is a well-known traditional Chinese medicine used to treat nocturia by tonifying and warming the kidney. Our recent clinical study found that overactive bladder (OAB) patients treated with cinnamon powder (CNP) patches exhibited significantly ameliorated OAB symptoms without significant side effects, but the mechanism of action is unclear. To explore the beneficial effects and action mechanisms of CNP and its major active component cinnamaldehyde (CNA) in an OAB-related murine model, cyclophosphamide- (CYP-) induced OAB injury was performed on male ICR mice in the presence or absence of CNP and CNA, as well as solifenacin, a clinical drug for OAB as a reference. Twenty-four-hour micturition patterns (frequency of urination and volume of urine per time), as well as histopathological examination, immunohistochemistry (IHC), and Western blotting of the bladder, were analyzed for mechanism elucidation. Administration of CYP (300 mg/kg, i.p.) induced typical OAB pathophysiological changes, including increased frequency of urination and reduced volume of urine. CYP-induced mice displayed strong edema of the bladder and hemorrhagic cystitis, accompanied by loss of normal corrugated folds and decreased muscarinic receptors (M2/M3) in the urothelium, and disordered/broken structures of the lamina propria and detrusor. These changes were correlated with increased leukocyte (CD11b) infiltration colocalized with inflammatory (pp65 NFκB, macrophage migration inhibitory factor (MIF)/Toll-like receptor 4 (TLR4)) and fibrotic (stem cell factor (SCF)/c-Kit, α-smooth muscle actin (α-SMA)/β-catenin) signals. Treatment with CNP (600 mg/kg, p.o.) and CNA (10–50 mg/kg, p.o.), but not solifenacin (50 mg/kg), 30 min after CYP induction significantly ameliorated CYP-induced dysfunction in micturition patterns and pathophysiological changes. CNP and CNA further suppressed MIF/TLR4-associated inflammatory and SCF/c-Kit-related fibrotic signaling pathways. Our findings indicate that suppression of inflammatory and fibrotic signals contributes to the crucial mechanism in the improvement of CYP-induced OAB by CNP and CNA.

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Piceatannol increases the expression of hepatocyte growth factor and IL-10 thereby protecting hepatocytes in thioacetamide-induced liver fibrosis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0001 ◽

2016 ◽

Vol 94 (7) ◽

pp. 779-787 ◽

Cited By ~ 6

Author(s):

Hazem Abd-Elgawad ◽

Nashwa Abu-Elsaad ◽

Amr El-Karef ◽

Tarek Ibrahim

Keyword(s):

Growth Factor ◽

Liver Fibrosis ◽

Liver Function ◽

Hepatocyte Growth Factor ◽

Transforming Growth Factor ◽

Histopathological Examination ◽

Smooth Muscle Actin ◽

Interleukin 10 ◽

Hepatocyte Growth ◽

Inflammatory Effect

Piceatannol is a polyphenolic analog of resveratrol that selectively inhibits the non-receptor tyrosine kinase-Syk. This study investigates the potential ability of piceatannol to attenuate liver fibrosis and protect hepatocytes from injury. Thioacetamide was injected in adult male mice (100 mg/kg, i.p., 3 times/week) for 8 weeks. Piceatannol (1 or 5 mg/kg per day) was administered by oral gavage during the last 4 weeks. Liver function biomarkers, tissue malondialdehyde (MDA), cytokeratin-18 (CK18), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were measured. Necroinflammation, fibrosis, expression of transforming growth factor (TGF)-β1, and α-smooth muscle actin (SMA) were scored by histopathological examination and immunohistochemistry. Obtained results showed ability of piceatannol (1 mg/kg) to restore liver function and reduce inflammation. It significantly (p < 0.001) reduced MDA, CK18, TGF-β1, and α-SMA expression, and increased HGF and IL-10. It can be concluded that piceatannol at low dose can inhibit TGF-β1 induced hepatocytes apoptosis and exerts an anti-inflammatory effect attenuating fibrosis progression.

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Sestrin 2 Attenuates Rat Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

Cellular Physiology and Biochemistry ◽

10.1159/000495829 ◽

2018 ◽

Vol 51 (5) ◽

pp. 2111-2122 ◽

Cited By ~ 7

Author(s):

Yi-Bing Hu ◽

Xiao-Ting Ye ◽

Qing-Qing Zhou ◽

Rong-Quan Fu

Keyword(s):

Liver Fibrosis ◽

Protein Expression ◽

Hepatic Fibrosis ◽

Transforming Growth Factor ◽

Histopathological Examination ◽

Stellate Cell ◽

Smooth Muscle Actin ◽

Mrna Levels ◽

Alpha Smooth Muscle Actin

Background/Aims: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. Methods: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-β (TGF-β) and in mice treated with carbon tetrachloride (CCl4), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. Results: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. Conclusion: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway.

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Anti-fibrosis effect for Hirsutella sinensis mycelium based on inhibition of mTOR p70S6K phosphorylation

Innate Immunity ◽

10.1177/1753425917726361 ◽

2017 ◽

Vol 23 (7) ◽

pp. 615-624 ◽

Cited By ~ 5

Author(s):

Huimin Yue ◽

Yarong Zhao ◽

Haining Wang ◽

Feiya Ma ◽

Fei Liu ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Lung Fibrosis ◽

Molecular Mechanisms ◽

Histopathological Examination ◽

Smooth Muscle Actin ◽

A549 Cells ◽

Mtor Pathway ◽

Cordyceps Sinensis ◽

Tgf Β1

Hirsutella sinensis, cultured in vitro, is an attractive substitute for Cordyceps sinensis as health supplement. The aim of this study was to demonstrate whether H. sinensis mycelium (HSM) attenuates murine pulmonary fibrosis induced by bleomycin and to explore the underlying molecular mechanisms. Using lung fibrosis modle induced by intratracheal instillation of bleomycin (BLM; 4 mg/kg), we observed that the administration of HSM reduced HYP, TGF-β1 and the production of several pro-fibrosis cytokines (α-smooth muscle actin, fibronectin and vimentin) in fibrotic mice lung sections. Histopathological examination of lung tissues also demonstrated that HSM improved BLM-induced pathological damage. Concurrently, HSM supplementation markedly reduced the chemotaxis of alveolar macrophages and potently suppressed the expression of inflammatory cytokines. Also, HSM influenced Th1/Th2 and Th17/Treg imbalance and blocked the phosphorylation of mTOR pathway in vivo. Alveolar epithelial A549 cells acquired a mesenchymal phenotype and an increased expression of myofibroblast markers of differentiation (vimentin and fibronectin) after treatment with TGF-β1. HSM suppressed these markers and blocked the phosphorylation of mTOR pathway in vitro. The results provide evidence supporting the use of HSM in the intervention of pulmonary fibrosis and suggest that HSM is a potential therapeutic agent for lung fibrosis.

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Intra-abdominal Solitary Myofibroma in a Child: A Rare Case Report

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/46644.14411 ◽

2021 ◽

Author(s):

Smita Singh ◽

Jyoti Garg ◽

Kusha Sharma ◽

Kiran Agarwal

Keyword(s):

Histopathological Examination ◽

Smooth Muscle Actin ◽

Iliac Fossa ◽

Correct Diagnosis ◽

Neck Region ◽

Abdominal Distension ◽

Malignant Tumours ◽

Rare Presentation ◽

Anaplastic Lymphoma ◽

Abdominal Masses

Intra-abdominal masses in children are usually malignant. Benign tumours at this location are not seen frequently. It is even rarer to find solitary myofibromas intra-abdominally as these tumours are known to have predilection for the head and neck region. We present an unusual case of solitary myofibroma with abdominal localisation in a six-year-old male child who presented with abdominal distension since six months. Computed Tomography (CT) abdomen revealed a complex solid-cystic mass extending from umbilicus to right iliac fossa and measuring 9×6×4 cm. Histopathological examination revealed a tumour displaying biphasic nodular pattern with the presence of lighter staining fascicles of mature myoid cells along with darker staining and more cellular areas of smaller primitive cells. On Immunohistochemistry (IHC), tumour cells were positive for vimentin and Smooth Muscle Actin (SMA) with variable reactivity for desmin while these were negative for CD34 and Anaplastic Lymphoma Kinase 1 (ALK). Based on the histopathological and immunohistochemical findings, final diagnosis of myofibroma was made. Recognition of these lesions is extremely challenging owing to their rare presentation intra-abdominally and also because of their close morphological overlap with other spindle cell tumours commonly found at this site. This case highlights the combined role played by histopathology and IHC in making a clear distinction between different entities. It is imperative for both clinicians and histopathologists to establish the correct diagnosis as excision of the solitary myofibroma is curative in most cases and offers better clinical course than the more commonly found malignant tumours at this site.

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Nigella sativa and Thymoquinone: A Natural Blessing for Periodontal Therapy

Antioxidants ◽

10.3390/antiox9121260 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1260

Author(s):

Mohamed Mekhemar ◽

Yasmine Hassan ◽

Christof Dörfer

Keyword(s):

Nigella Sativa ◽

Periodontal Regeneration ◽

Periodontal Therapy ◽

Periodontal Treatment ◽

Oral Diseases ◽

Active Constituent ◽

Beneficial Effects ◽

Action Mechanisms ◽

Clinical Experiments

Thymoquinone (TQ), the chief active constituent of Nigella sativa (NS), shows very valuable biomedical properties such as antioxidant, antimicrobial, anticancer, anti-inflammatory, antihypertensive, hypoglycemic, antiparasitic and anti-asthmatic effects. Several studies have examined the pharmacological actions of TQ in the treatment of oral diseases but its potential role in periodontal therapy and regeneration is not yet fully defined. The present investigation has been designed to review the scientific studies about the effects of TQ as an adjunct to periodontal treatment to promote healing and periodontal regeneration. Along with clinical experiments, in vitro studies exhibit the beneficial effects of TQ during periodontal therapy. Nevertheless, additional comprehensive clinical and preclinical studies at cellular and molecular levels are essential to examine the particular action mechanisms of Nigella sativa and its elements, particularly TQ, during periodontal treatment or regeneration.

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Botulinum Toxin Use in the Lower Urinary Tract

The Scientific World JOURNAL ◽

10.1100/tsw.2007.150 ◽

2007 ◽

Vol 7 ◽

pp. 808-817

Author(s):

Shelby N. Morrisroe ◽

Michael B. Chancellor

Keyword(s):

Botulinum Toxin ◽

Urinary Tract ◽

Overactive Bladder ◽

Lower Urinary Tract ◽

Botulinum Neurotoxin ◽

Botulinum Toxins ◽

Muscle Paralysis ◽

Botulinum Neurotoxin A ◽

Beneficial Effects ◽

Lower Urinary

Botulinum toxins are well known for their ability to disrupt neurotransmission and cause muscle paralysis. Recently, urologists have discovered their beneficial effects in patients with neurogenic and overactive bladder conditions. This review is intended to provide a quick overview for urologists of the structure, function, and clinical uses of botulinum neurotoxin A in the lower urinary tract.

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An Unusual Presentation of Leiomyosarcoma Posing a Diagnostic Dilemma: A Case Report

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/46383.14306 ◽

2020 ◽

Author(s):

Smita Singh ◽

Kusha Sharma ◽

Vipan Kumar ◽

Partap Yadav

Keyword(s):

Smooth Muscle ◽

Head And Neck ◽

Histopathological Examination ◽

Smooth Muscle Actin ◽

Correct Diagnosis ◽

Neck Region ◽

Temporal Region ◽

Diagnostic Dilemma ◽

First Case ◽

Painless Mass

Leiomyosarcoma (LMS) is a malignant tumour of smooth muscle origin commonly seen in genital and gastrointestinal location. However, its presence in the head and neck region in a young child is extremely rare. Authors present a unique case of LMS in a one year and five-month-old child who presented with a painless mass in the right temporal region of the head. Histopathological examination revealed a highly cellular tumour arranged in intersecting fascicles of spindle cells with brisk mitotic activity and interspersed areas of necrosis. On Immunohistochemistry (IHC), the tumour cells were positive for Smooth Muscle Actin (SMA), Desmin and Vimentin and negative for S100 and Myogenin. A diagnosis of LMS was thus, made. Head and neck sarcoma is a broad entity encompassing plethora of differentials with closely overlapping morphological features which renders them diagnostically challenging, this can be resolved by employing various immunohistochemical stains readily available in all laboratories. This case highlights the combined role played by histopathology and immunohistochemistry in arriving at the correct diagnosis. To the best of our knowledge, this is the first case of LMS reported in the temporal region of head and is distinct with respect to its rare incidence, location and age at presentation. LMS at this site may masquerade as deceptively benign painless mass and may not be suspected initially, however one should bear in mind that these are moderate-to-high grade tumours and any delay in management may portend poor prognosis. Timely and aggressive surgical management is thus, the mainstay of treatment and critical to patient survival.

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Biopsy of small salivary glands in the diagnosis of Mikulicz-Sjögren's syndrome

Vojnosanitetski pregled ◽

10.2298/vsp0206615i ◽

2002 ◽

Vol 59 (6) ◽

pp. 615-620 ◽

Cited By ~ 1

Author(s):

Srbislav Ilic ◽

Ljubisa Arsic ◽

Ivica Milosavljevic ◽

Miroslav Strbac ◽

Gordana Tomasevic

Keyword(s):

Salivary Glands ◽

Diagnostic Criteria ◽

Clinical Laboratory ◽

Histopathological Examination ◽

Smooth Muscle Actin ◽

Tissue Destruction ◽

Lacrimal Glands ◽

Lower Lip ◽

Golden Standard ◽

Diagnostic Work

Background. Sj?gren's syndrome (SS) represents autoimmune disease characterized by chronic inflammation, destruction and insufficiency of exocrine glands, particularly salivary and lacrimal glands, accompanied by dryness of mouths and eyes. Diagnostic work-up involves clinical laboratory tests, radiography, scintigraphy and bioptic histopathological examination. Examination of small salivary glands in the biopsy of the lower lip represents a 'golden standard' of diagnosis of SS, concerning the fact that the growth and the disfunction of salivary and lacrimal glands occurs in different pathologic states. Methods. Resected specimens of the lower lip were obtained from 47 patients with clinical diagnosis of SS. After standard histopathological treatment, slices were hematoxylin and eosin stained. Immunohistochemistry against smooth muscle actin was performed using LSAB+ method (AHSMA-M7558, DAKO 1:50). On the basis of generally accepted histopathological diagnostic criteria the results were categorized as: findings suspicious for SS; findings compatible with the diagnosis of SS (mild, moderate and high degree of inflammation); nonspecific inflammatory reaction and nonrepresentative biopsy samples. Results. Diagnosis of SS was confirmed in 32% of cases. In 2% of cases findings were suspected for SS, in 36% of cases findings were compatible with the diagnosis of nonspecific inflammation, and in 30% of cases material was not representative. Conclusions. By the biopsy of salivary glands of the lower lip the diagnosis of SS was confirmed in 50-60% of cases. Upon the precise diagnostic criteria it was also possible to determine the intensity of inflammation and tissue destruction in SS and identify other pathological conditions, which justified the biopsy. Surgical technique had to be adequate in order to obtain representative number of small salivary glands. In the presented material 30% of specimens were nonrepresentative which was very high percentage compared with literature data. This was most probably the reason why the diagnosis of SS was confirmed in only 32% of cases, i.e., in every third patient.

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Angioleiomyoma of the Uterus with Extensive Hyaline Degeneration- A Rare Case Report with Brief Review of Literature

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/48041.14695 ◽

2021 ◽

Author(s):

Devi Subbarayan ◽

Vijayashree Raghavan ◽

Priyadharshini Kumar ◽

Vijayalakshmi Kandasamy

Keyword(s):

Rare Case ◽

Soft Tissues ◽

Histopathological Examination ◽

Smooth Muscle Actin ◽

Broad Ligament ◽

Female Genital Tract ◽

Cervix Uterus ◽

Abnormal Uterine Bleeding ◽

Review Of Literature ◽

Vascular Component

Angioleiomyoma (AL) or vascular leiomyoma is a distinct variant of leiomyoma with prominent vascular component, usually occurs in extremities very rarely arise in internal organ. It has been documented in female genital tract including cervix, uterus, ovary and broad ligament. Uterine leiomyoma is very rare and distinct variant of conventional leiomyoma which has prominent vascular component. The diagnosis of this variant requires histopathological examination since it does not have specific clinical and radiological features unlike in soft tissues where it presents as subcutaneous painful swelling. Like conventional leiomyomyoma, AL can also undergo degenerative changes like hyalinisation, infarction, calcification and myxoid change. Here, a rare case of uterine AL with ovarian seromucinous cystadenoma is reported in a 38-year-old female who was diagnosed incidentally when she was evaluated for abnormal uterine bleeding. MRI pelvis revealed a intramural fibroid of size 5×4.5 cm noted in anterolateral myometrium of uterus and a large multiloculated cystic lesion of size 12.5×12.5×8.8 cm seen arising from left ovary. Abdominal hysterectomy was done. Grossly, sectioning of myometrium showed well circumscribed grey white to grey brown intramural fibroid measuring 4.5×3.5 cm. Histologically the lesion showed fascicles of spindle cells swirling around the thick walled blood vessels and immunohistochemically these cells were positive for Smooth Muscle Actin (SMA). Here, this rare case of uterine AL with brief review of literature is reported.

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Beneficial Effects of Fennel (Foeniculum Vulgare) in Treating Obesity in Rats

Journal Of Obesity Management ◽

10.14302/issn.2574-450x.jom-18-2484 ◽

2019 ◽

Vol 1 (2) ◽

pp. 16-33 ◽

Cited By ~ 2

Author(s):

Nawal A. A. Elghazaly ◽

Eman H. Radwan ◽

Hala H. Zaatout ◽

Mohamed M. Elghazaly ◽

Nour El din Allam

Keyword(s):

Total Protein ◽

Histopathological Examination ◽

Insulin Resistance Syndrome ◽

Serum Levels ◽

Herbal Remedies ◽

Control Group ◽

Albino Rats ◽

Oxidative Stress Biomarkers ◽

Foeniculum Vulgare ◽

Beneficial Effects

Obesity is associated with a number of serious medical complications, which are often referred to as the “insulin resistance syndrome”. The aim of the present study was performed to investigate the possible interaction between a conventional drug used for management of cholesterol and traditional herbal remedies on the obesity. This was carried through out: through estimation of blood test; Estimation of serum tests; Determination of oxidative stress biomarkers and the antioxidant enzymes activities in the liver were assayed; Histopathological examination of the liver and kidney of adult male albino rats were done. In the present study, the serum levels of the total protein and albumin in the obesity group (7.1± 0.2) and (4.78 ± 0.19); respectively were significantly (p ≤ 0.05) more than those of the control group (6.5±0.1) and (3.95± 0.1).The administration of (fennel group) revealed significant (P<0.05) decrease in the serum levels of the albumin and total protein (4.38± 0.1) and (6.65± 0.2); respectively as compared to the obesity group (4.78 ± 0.19) and (7.1± 0.2(. The total cholesterol of the group(5) (fennel and ator) after two weeks from a high fat diet than treatment with fennel and Ator through six weeks equal 142.86±5.9, 100.4±8.68, 93.29±5.99, 87.1±11.28, 80.4±21.55, 78.1±6.7 and 77.1±6.87; respectively. The present study showed a significant (P<0.05) increase in the activities of ALT, AST and ALP in the obesity group which recorded as (60.5±11.45), (57.25±6.3) and (845.0±49.47); respectively as compared to the control group (28.25±1.7), (38.5±3.87) and (537.0±41.5); respectively. The fennel group caused significant decrease in the activities of these enzymes (41.0± 2.9), (42.25+3.2) and (717.75+48.6); respectively compared to the obesity group. Ator group showed a significant decrease in the activities of these enzymes (40.0±2.16), (42.5±3.1) and (679.25±41.16); respectively compared as obesity group. The activity of AlT, AST and ALP in the fennel and ator group (32.75±2.5), (40.5±2.38) and (601.25±17.5); respectively were near to the control group.

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