The Effect of Glycyrrhizin on the Viability and Proliferation of Dental Pulp Stem Cells Compared to Intracanal Medicaments.

AIM: To study the effect of glycyrrhizin (GA) on the viability and proliferation of dental pulp stem cells (DPSCs) compared with intracanal medicaments. MATERIALS AND METHODS: Third molars of an adult donor were used to obtain the DPSCs. Flow cytometry was utilized to conduct phenotypic analysis for DPSCs. The methyl-thiazol tetrazolium (MTT) test was used to detect the cell viability. Cell proliferation assay was conducted at distinct time intervals: 3, 5, and 7 days. RESULTS: The flow cytometry analysis verified the positive expression of mesenchymal cell surface antigen molecules (CD73, CD90, and CD105) and the absence of hematological markers (CD14, CD34, and CD45) in the DPSCs. The cells that treated with concentrations more than 0.5 mg/mL of Ca(OH2) and triple antibiotic paste (TAP) gave significant decrease in viability in comparison to the untreated cells (p < 0.05). Also, the cells treated with concentrations 50 and 25 µM of GA showed no significant difference compared with the untreated cells (p > 0.05), while concentrations 12.5 and 6.25 µM expressed a significant increase in viability compared with the untreated cells (p < 0.05). At 7 days, cells treated with the three different concentrations of GA (12.5, 25, and 50 µM) demonstrated a significant increase in cell density compared with Ca(OH)2 and TAP-treated cells (p < 0.05). CONCLUSION: Based upon the potential of GA on DPSCs proliferation compared with Ca(OH)2 and TAP, It is conceivable to acknowledge that GA could be used as an intracanal medicaments for revascularization process of necrotic immature teeth. CLINICAL SIGNIFICANCE: This study emphasizes the significance of assessing alternative root canal medicaments and their impact on the proliferation and viability of DPSCs. The results regarding GA, specifically its impact on the viability and growth of DPSCs, provide essential understanding for its potential application as an intracanal medicine. This study adds to the continuous endeavors in identifying safer and more efficient intracanal therapies, which are essential for improving patient outcomes in endodontic operations. How to cite this article: Alrashidi MA, Badawi MF, Elbeltagy MG, et al. The Effect of Glycyrrhizin on the Viability and Proliferation of Dental Pulp Stem Cells Compared to Intracanal Medicaments. J Contemp Dent Pract 2024;25(3):267-275.

Modulation of CXCL10 activity as a therapeutic target of ocular toxoplasmosis in diabetic mice.

Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.

Examining the Effects of Asiaticoside on Dental Pulp Stem Cell Viability and Proliferation: A Promising Approach to Root Canal Treatment.

AIM: This study aims to evaluate the impact of asiaticoside (AC) on the viability and proliferation of dental pulp stem cells (DPSCs), considering the known negative effects of routinely used intracanal medicaments. This evaluation will be compared with the outcomes from using traditional intracanal medicaments, specifically triple antibiotic paste (TAP) and calcium hydroxide [Ca(OH)2]. MATERIALS AND METHODS: The DPSCs were obtained from the third molars of an adult donor. The application of flow cytometry was employed to do a phenotypic analysis on DPSCs using CD90, CD73, CD105, CD34, CD14, and CD45 antibodies. The methylthiazol tetrazolium (MTT) assay was employed to assess cellular viability. The cells were treated with different concentrations of TAP and Ca(OH)2 (5, 2.5, 1, 0.5, and 0.25 mg/mL), along with AC (100, 50, 25, 12.5, and 6.25 µM). A cell proliferation rate was performed at 3, 5, and 7 days. RESULTS: The characterization of DPSCs was conducted by flow cytometry analysis, which verified the presence of mesenchymal cell surface antigen molecules (CD105, CD73, and CD90) and demonstrated the absence of hematopoietic markers (CD34, CD45, and CD14). Cells treated with concentrations over 0.5 mg/mL of TAP and Ca(OH)2 showed a notable reduction in cell viability in comparison to the untreated cells (p < 0.05). Additionally, the cells treated with different concentrations of AC 12.5, 6.25, 25, and 50 µM did not differ significantly from the untreated cells (p > 0.05). Nevertheless, cells treated with concentrations of 100 µM showed a significant reduction in viability compared to the untreated cells (p < 0.05). After a period of 7 days, it was noted that cells exposed to three different concentrations of AC (50, 25, and 12.5 µM) had a notable rise in cell density in comparison to TAP and Ca(OH)2 (p < 0.05). Furthermore, cells that were exposed to a concentration of 12.5 µM exhibited the highest cell density. CONCLUSION: The cellular viability of the AC-treated cells was superior to that of the TAP and Ca(OH)2-treated cells. Moreover, the AC with a concentration of 12.5 µM had the highest degree of proliferation. CLINICAL SIGNIFICANCE: This study underscores the importance of evaluating alternative root canal medicaments and their effects on DPSCs' growth and vitality. The findings on AC, particularly its influence on the survival and proliferation of DPSCs, offer valuable insights for its probable use as an intracanal medication. This research contributes to the ongoing efforts to identify safer and more effective intracanal treatments, which are crucial for enhancing patient outcomes in endodontic procedures. How to cite this article: Alazemi MJ, Badawi MF, Elbeltagy MG, et al. Examining the Effects of Asiaticoside on Dental Pulp Stem Cell Viability and Proliferation: A Promising Approach to Root Canal Treatment. J Contemp Dent Pract 2024;25(2):118-127.

Cerebral Radiation-Induced Vasculopathy Mimicking Primary Central Nervous System Vasculitis.

Cranial irradiation is one of the main treatment modalities for tumors of the CNS. However, it can lead to significant damage to the treated region. Among the late complications of radiation therapy to the brain is vasculopathy of the small and/or large arteries. In this article, we report a case of CNS radiation-induced vasculopathy presenting 30 years after cranial irradiation and mimicking primary CNS vasculitis. The present case illustrates the importance of monitoring and carefully evaluating delayed side effects of radiotherapy as well as emphasizes the importance of obtaining a detailed history of any patient presenting with sudden unexplained symptoms. If a complete proper history of the patient's past medical diagnoses and procedures was taken, medical professionals would not have needed to conduct extensive investigations and implement treatment plans for a less likely diagnosis, in this case, aggressive treatment of a possible primary CNS vasculitis with high-dose steroids. Therefore, it is imperative to raise the possibility of radiation-induced vasculopathy after excluding all possible causes of deterioration in patients with a history of cranial radiation therapy.

Ivermectin modulated cerebral γ-aminobutyric acid (GABA) and reduced the number of chronic Toxoplasma gondii cysts significantly in the brains of immunocompromised mice.

Disruption of GABAergic signaling could exaggerate the inflammatory reaction associated with Toxoplasma gondii infection, as well as produce neurophysiological consequences including seizures that occur within the brain tissues. The current study aimed to evaluate the efficacy of ivermectin (IVM) in treating latent cerebral toxoplasmosis and define its role in the neuromodulation of cerebral tissue GABA expression, conducted in an immunocompromised dexamethasone-treated mouse model infected with the ME49 Toxoplasma strain. The control (non-infected non-treated) group showed a mean of 22.1 ± 0.71 for local expression of GABA. Significantly lower expression (3.78 ± 1.38) was recorded in the infected non-treated group (p ≤ 0.05). On the contrary, a significantly higher expression was reported in the group infected and treated with IVM than in the infected non-treated group (19.8 ± 0.8). While the infected spiramycin (SP)-treated group reported a significantly lower level than the control. Non-infected groups that received only IVM or SP recorded 22.3 ± 0.45 and 22 ± 0.89 respectively with no significant difference. IVM is shown in this work, not only to reduce the size and the number of Toxoplasma cystic lesions within the brain significantly with a reduction rate of 68.85% but to also increase the level of GABA local expression significantly in addition to improving cerebral histopathology. Thus, IVM by its ability to modulate GABA expression may improve such clinical situations, if used as a treatment either exclusively or in combination with other medications.

A novel intra-tumoral drug delivery carrier for treatment of oral squamous cell carcinoma.

The treatment of oral squamous cell carcinoma (OSCC) includes systemic chemotherapy and is associated with aggressive side effects on patients. This study evaluated a new intra-tumor-targeted drug delivery method for the treatment of OSCC induced on the dorsum of the tongue in white mice. The induced tumors were examined by needle biopsy. A targeted anticancer drug (Cetuximab) and [Cisplatin and 5 Fluorouracil (5-FU)] chemotherapeutic agents were loaded on polyethylene glycol-polylactide-polyethylene glycol (PEG-PLA-PEG) nanoparticles (NPs) designed for intralesional injection while systemic administration was used as control. Fourier transform infrared spectroscopy (FTIR) was performed to study NP chemical structure, a drug release profile was conducted to study release kinetics, and histopathological evaluation was performed before and after treatment to evaluate tissue reactions (n-28, ά = 0.05). The drug release profile was characteristic of the chemotherapeutic agent showing early quick ascend followed by sustained slow release. FTIR peaks identified the polymeric structure of the drug nano-carrier. Histopathologic examination of chemically induced OSCC revealed different grades ranging from non-invasive to invasive stages of OSCC. Intra-tumoral test group revealed significant remission of observed cancer grade compared to the systemically administered group (X2 = 12.63, P < 0.001). Finally, using synthesized PEG-PLA-PEG NPs for intralesional injection is a promising route for the treatment of OSCC.

Bonding durability and remineralizing efficiency of orthodontic adhesive containing titanium tetrafluoride: an invitro study.

BACKGROUND: Titanium tetrafluoride has been shown to protect tooth enamel from demineralization. This study investigated the effect of incorporating different concentrations of TiF4 (1, 2 and 3 Wt.%) into an orthodontic primer on the shear bond strength of orthodontic brackets and the enamel microhardness after cariogenic challenges. METHODS: Three different TiF4 concentrations (1, 2 and 3 Wt.%) were prepared and added to the etch and rinse orthodontic primer. Ninety freshly extracted premolars were randomly divided into five groups according to the experimental primers and ageing conditions: TF0, TF0C, TF1C, TF2C, and TF3C. The TF0C group had no TiF4 in the primer, while TF1C, TF2C, and TF3C had 1, 2 and 3 Wt.% TiF4 in the primer, respectively. In the TF0 group, specimens were immersed in deionized water for 24 h as a control group, while all other groups were immersed in a demineralizing solution for 28 days. Each of the five groups was divided into two subgroups: The first group was subjected to shear bond strength and adhesive remnant index testing (N = 50 teeth, 10/group), while the second group was subjected to enamel surface microhardness testing (N = 25 teeth, 50 tooth halves, 10 tooth halves/group). Fifteen teeth (N = 15 teeth, n = 3/group) representing the five groups were subjected to SEM and microelemental analysis (EDX). SBS, ARI, microhardness, and Ca/P ratio were measured, and the data were analyzed using ANOVA and Tukey's tests. RESULTS: The TF2C group had the highest SBS value (9.93 ± 1.23), while the TF0C (5.24 ± 0.65) and TF3C (5.13 ± 0.55) had the lowest SBS values. The enamel microhardness in the TF0C group was significantly reduced (p < .001). Enamel microhardness values were significantly (p < .001) higher in groups TF1C, TF2C, and TF3C than in TF0C. The highest Ca/P ratio was significantly recorded for the TF2C group (2.65 ± 0.02). CONCLUSIONS: Incorporation of 1 and 2 Wt.% TiF4 into the orthodontic primers showed adequate bond strength and better remineralization effect. However, 1 Wt.% TiF4 showed lower ARI values than 2 Wt.% TiF4.

Type-1 diabetes mellitus down-regulated local cerebral glial fibrillary acidic protein expression in experimental toxoplasmosis.

Cerebral toxoplasmosis is an opportunistic infection, occurring mostly in immunosuppressed patients due to the reactivation of latent Toxoplasma cysts. The cerebral comorbidity in diabetic patients tends to intensify the burden of pathogenic infection within the brain. The aim of this work was to study the effect of cerebral toxoplasmosis in experimentally infected hyperglycemic mice, on histopathology and glial fibrillary acidic protein (GFAP) expression, compared to normoglycemic mice at different time intervals. Vasculopathy was exclusively observed in diabetic groups, with features of increased severity during Toxoplasma infection. Gliosis was observed in diabetic groups, while hyperactive astroglial activity was detected in normoglycemic groups, especially at 6 weeks of infection. GFAP expression showed significant up-regulation in normoglycemic mice at 6 weeks of infection (40.03 ± 1.41) afterwards, it decreased to 22.22 ± 3.14 at 12 weeks which was statistically insignificant to the normal level, possibly indicating the successful Toxoplasma stage transformation (to bradyzoite), thereby limiting the infection within the brain. In hyperglycemic infected groups, GFAP was significantly down-regulated, in both acute and chronic phases of infection, most likely indicating failure of stage transformation and infection limitation. This may expose those vulnerable groups to the risk of dissemination, resulting in life-threatening diffuse encephalitis. The current study emphasized the importance of rapid diagnosis of Toxoplasma infection in diabetic subjects, and highlighted the value of using GFAP as a neurological indicator of disease progression in those comorbid cases.

Effect of Boswellic Acid on Viability of Dental Pulp Stem Cells Compared to the Commonly Used Intracanal Medications: An In Vitro Study.

AIM: This study was aimed at evaluating the effect of acetyl-11-keto-ß-boswellic acid (AKBA) on dental pulp stem cells (DPSCs) viability and proliferation to be used as a potential root canal medicament. MATERIALS AND METHODS: Dental pulp stem cells were isolated from human third molars. The phenotypic characterization of DPSCs was verified by flow cytometry analysis. The viability assay was performed using the methyl-thiazoltetrazolium (MTT) assay. Cells were treated with different concentration of triple antibiotic paste (TAP) and calcium hydroxide Ca(OH2) (5, 2.5, 1, 0.5, and 0.25 mg/mL), AKBA (10, 5, 1, 0.1, and 0.01 µM). All experiments were done in separate triplicate experiments. Results: Dental pulp stem cells were characterized by flow cytometry. Cells treated with Ca(OH)2 (1, 2.5, and 5 mg/mL) showed significantly reduced viability compared with the control cells (p < 0.05). Dental pulp stem cells treated with 1, 2.5, and 5 mg/mL TAP resulted in a significant decrease in viability (p < 0.05). Cells treated with AKBA in concentrations (1, 0.1, and 0.01 µM) demonstrated higher viability than the control group (p < 0.05), while AKBA in concentrations (5 and 10 µM) showed equal or decreased viability than the control group. (p > 0.05). Regarding cell density assay, AKBA showed significant increase in cell density after 5 and 7 days compared with cells medicated with TAP and Ca(OH)2 while TAP revealed marked reduction in cell density in all the tested intervals. CONCLUSION: Acetyl-11-keto-ß-boswellic acid in lower concentrations (0.01, 0.1, and 1 µM) demonstrated superior cell viability than TAP and Ca(OH)2, and it may possess the potential to be an intracanal medicament in regenerative endodontics. CLINICAL SIGNIFICANCE: Studying the effect of different potential root canal medicaments and their capability to induce DPSCs proliferation might be of value. The influence of AKBA on the viability and proliferation of DPSCs tested in this study sheds light on its use as a potential intracanal medication especially in regenerative endodontics. How to cite this article: Amer NA, Badawi MF, Elbeltagi MG, et al. Effect of Boswellic Acid on Viability of Dental Pulp Stem Cells Compared to the Commonly Used Intracanal Medications: An In Vitro Study. J Contemp Dent Pract 2023;24(12):957-966.

The disease course of multiple sclerosis before and during COVID-19 pandemic: A retrospective five-year study.

INTRODUCTION: COVID-19 pandemic is thought to influence the natural history of immune disorders, yet the knowledge on its effect on multiple sclerosis (MS) is unknown and not fully understood for which we conducted this retrospective study. METHODS AND MATERIALS: We included all patients with MS seen in King Faisal Specialist Hospital and Research Centre in Jeddah, Saudi Arabia, between January 2017 and October 20201. We determined clinical and radiological evidence of disease activities in all patients by the end of the study period, and we compared the disease patterns before and during the pandemic. We also identified patients with COVID-19 since March 2020, who had at least 3 months of follow-up following the infection. RESULTS: We studied 301 patients; 216 (72%) were women, the mean age was 38 years (range; 16, 73 years), the mean disease duration was 10 years (range; 1, 36 years), and the median EDSS score was 0.5 (range; 0, 8). RRMS accounted for most of the cases (270 patients). MS disease activities were 25% less prevalent during the pandemic compared to the preceding 3 years (26 vs. 51%, respectively, p < 0.01). Bivariate analysis showed significant higher disease activities in patients younger than 35 years (73 vs 27%), on DMT (68 vs 32%), and complaint to therapy (69 vs 31%). Multiple logistic regression analysis showed that the likelihood of MS disease activities were 3 times more during the pre-pandemic era (adjusted OR = 3.1, p value < 0.05, 95% CI; 1.4, 7.1). Thirty patients (10%) were infected with COVID-19. All patients reported mild symptoms, and none required hospitalization. COVID-19 was prevalent among younger patients with RRMS, with low EDSS scores, irrespective of DMTs they received. COVID-19 infection was not associated with clinical relapses or MRI changes. Disease activities were dependent on DMT use and not COVID-19 status. Multivariate analyses also confirmed no effect of COVID-19 on disease activities (p = 0.3 and 0.4, for clinical and MRI changes, respectively). CONCLUSIONS: MS disease activities did not increase during the pandemic, yet the apparent decrease in the disease activities is probably due to under reporting and not a real decrease in disease activities because of the pandemic. The COVID-19 infection in our MS patients showed a benign disease course, yet standard precautions to reduce the risk of COVID-19 transmission should be applied accordingly.

Urine-Derived Stem Cells Versus Their Lysate in Ameliorating Erectile Dysfunction in a Rat Model of Type 2 Diabetes.

Background: Diabetic erectile dysfunction (DED) is a significant consequence of diabetes mellitus, and it is a multifactorial phenomenon that has no definitive treatment until now. Many therapeutic options provide symptomatic improvement rather than addressing the underlying etiology or restoring normal function. Stem cell (SC) therapy represents a potential hope in DED management. It is well established that the regenerative effect of stem cells can be attained by their paracrine action and their ability to differentiate into many cell lineages, including endothelial and smooth muscle cells. Hence, we tried to compare the effects of transplantation of urine-derived stem cells (USCs) or their lysate (USC-L) into the corpora cavernosa (CCs) of rats with DED. Materials and Methods: A total of 55 adult male Wistar rats were included in this study. USCs were obtained from ten healthy rats. Another ten rats did not subject to any intervention and served as a control (group I). Type 2 DM and DED were induced in the remaining 35 rats, but DED was tested and proved in only 24 rats, which were randomly divided into three groups (n = 8 in each). The DED group (group II) and either USCs (2 × 106 cells) or their lysate (200 µl) were transplanted into the CCs of each rat in the other two groups (groups III and IV), respectively. Results: Although the DED rats exhibited deterioration in all copulatory functions as compared to the control group, our histopathological, immunohistochemical, and morphometric results revealed that both USCs and USC-L have significantly restored the cavernous spaces, the ultrastructures of the endothelium that line the cavernous spaces, collagen/smooth muscle ratio, and the mean area percentage of α-SMA in the CCs as compared to DED rats. A respectable number of USCs was detected in the CCs of group III at the 4th week after transplantation, but this number significantly declined by the 8th week. Conclusion: Both USCs and USC-L can repair the structure and ultrastructure of CCs and improve the copulatory functions in the DED rat model. However, USC-L could be better used in DED to guard against the strange behavior of USCs after transplantation and their decreased survivability with time.

Efficacy of clofazimine and nitazoxanide combination in treating intestinal cryptosporidiosis and enhancing intestinal cellular regeneration in immunocompromised mice.

Cryptosporidium is a widely distributed food and water-borne enteric protozoan that affects a wide range of vertebrates, resulting in life-threatening consequences, particularly in immunocompromised hosts. The lack of effective anti-cryptosporidial drugs may be related to the parasite's unique intestinal location, plus the lack of studies on the process by which the protozoan is able to impair intestinal cellular function. The present work aimed to assess the effect of clofazimine (CFZ), an FDA-approved drug for the treatment of leprosy, as an anti-cryptosporidial drug, using transmission electron microscopy (TEM) and an immunocompromised mouse model. The affected intestinal mucosa with parasitic stages in the infected non-treated group showed signs of severe cellular degeneration, including the loss of tight junctions, deformed and damaged microvilli and irregularly distributed nuclei with a severely vacuolated cytoplasm. Comparatively, nitazoxanide (NTZ) monotherapy showed the lowest efficacy as the drug was associated with the lowest rate of oocyst shedding. In addition, NTZ treatment failed to achieve the return of complete cellular function; abnormalities were evident in the microvilli, cytoplasmic organelles and nuclear features. Clofazimine demonstrated an improvement of the mucosal cellular components, including mitochondria and significantly reduced oocyst shedding. Combined treatment with low-dose CFZ and half-dose NTZ resulted in a significant improvement in the enterocyte cellular structures with an absence of intracellular parasitic stages. These results indicate that CFZ, a safe and readily prescribed drug, effectively reduces cryptosporidiosis when used in combination with only half the dose of NTZ. Used in combination, these drugs were shown to be efficient in regaining intestinal cellular activity following Cryptosporidium-induced functional damage in an immunocompromised mouse model.

Antiparasitic and immunomodulating effects of nitazoxanide, ivermectin and selenium on Cryptosporidium infection in diabetic mice.

The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

Effect of mast cell stabilization on angiogenesis in primary and secondary experimental Trichinella spiralis infection.

BACKGROUND: Mast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators. The aim of this study was to explore the effect of the mast cell stabilizer (MCS), ketotifen, with and without albendazole, an anti-parasitic prescription medicine, on the inflammatory response against Trichinella spiralis, with the overall aim to investigate its effect on angiogenesis accompanying nurse cell formation. METHODS: The effect of ketotifen and albendazole was explored in eight groups of female BALB/c mice. Four groups were sensitized with a small dose of T. spiralis larvae. The drug regimen was then applied to both sensitized (challenged) and non-sensitized mice. The parasite load was assessed by histopathological examination of the small intestine and muscle tissue, and angiogenesis was assessed by immunohistochemistry to determine the expression of vascular endothelial growth factor (VEGF). RESULTS: Sensitized mice showed a significantly lower parasite load and a more pronounced inflammatory response than mice receiving a single infective dose of T. spiralis larvae. All treated groups showed a significant reduction in parasite count compared to the control groups (groups IAa and IBa), reaching approximately an 98.8% reduction in adult parasite count in the sensitized group treated with albendazole (groups IIAb and IIBb). MCS significantly decreased the parasite count during both the intestinal or muscular phases, reduced tissue inflammation, and decreased local VEGF expression, both in the non-sensitized and sensitized groups. CONCLUSION: Sensitization with a low dose of T. spiralis larvae was found to confer a partial protective immunity against re-infection and to positively affect the study outcomes, thus underlining the importance of vaccination, but after extensive studies. The anti-angiogenic effect of MCS protects against larval encystation during the muscle phase. The anti-angiogenic potential of albendazole suggests that the action of this anti-helminthic during trichinellosis is not confined to structural damage to the parasite cuticle but includes an effect on host immunopathological response.

Punica granatum and amygdalin extracts plus cobalamin combined with albendazole reduce larval burden and myositis in experimental trichinosis.

Trichinellosis is a zoonosis results from eating raw or semi-cooked meat of infected animals. Medicinal plants have been used lately as alternatives and/or combined therapies to resolve some drawbacks of the current regimens. This work analyzed the effect of albendazole monotherapy on Trichinella spiralis experimental infection (group A), in comparison to P. granatum and amygdalin extracts +cobalamin (group B), plus its combination with albendazole (group C). The study revealed that the extracts alone or combined with albendazole had an inferior effect to albendazole monotherapy regarding number of adult worms (40.83 ±3.82, 18.67 ±1.86 and 16.83 ±2.32, respectively). However, their effect was more obvious in muscle phase combined with albendazole, achieving the lower number of larvae/mL tissue homogenate (22.33 ±3.27 in comparison to 39.67 ±2.58 achieved by albendazole monotherapy). The extracts exerted a significant immunomodulatory effect by reducing the local CD4+ expression in the intestine as well as in muscle phase (1.15 ±0.25 and 3.80 ±0.65 in comparison to 4.97 ±0.37 and 12.20 ±0.87 with albendazole monotherapy, respectively). So, these extracts improved the therapeutic efficacy of albendazole, specifically in muscle phase and counteracted the inflammatory reaction caused by albendazole monotherapy, thus extensively alleviating the resulting myositis.

Antiproliferative, Apoptotic Effects and Suppression of Oxidative Stress of Quercetin against Induced Toxicity in Lung Cancer Cells of Rats: In vitro and In vivo Study.

In the present study, quercetin was examined against lung human cancer cells using A549 and H69 cancer cell lines in addition to normal non cancer cells (W138). Two genes Bax and Bcl-2 that play an important role in apoptosis pathways were investigated. Also Immunohistochemical study for caspase-3 which is considered as indicator for apoptosis was performed. Quercetin showed good anti proliferative activity against tested lung cancer cell lines, IC50 values on A549 are 8.65, 7.96 and 5.14 µg/ml at 24, 48 and 72h respectively. Also significant effects of quercetin on Bax, Bcl-2 and caspase-3 were observed, that can prove its ability to induce apoptosis. On the other hand quercetin showed good therapeutic effects against cyclophosphamide induced lung toxicity that were observed in the histopathology study. In vitro studies were also performed such as cell cycle analysis through flowcytometry. The obtained results from all these performed analysis proved that quercetin can induce apoptosis in human lung cancer cells, additionally quercetin showed ability to reduce MDA and increase SOD and GSHP levels which indicates its ability in suppressing oxidative stress, Quercetin has played a therapeutic role in cyclophosphamide induced lung toxicity as it has improved restoring of the damaged lung tissue as discussed in this research work.

Therapeutic Effect of Murine Bone Marrow-Derived Mesenchymal Stromal/Stem Cells and Human Placental Extract on Testicular Toxicity Resulting from Doxorubicin in Rats.

Oncotherapeutics like doxorubicin can affect male gonads; as a result, it leads to infertility. This work was conducted to demonstrate the toxic effects of doxorubicin on testes of male albino rats. Fifty male albino rats aged 5-7 weeks were used in this study. The animals were randomly separated into 5 sets (each set containing ten rats). Group I received saline (i.p.) for 4 weeks. Group II was given doxorubicin (DOX), 5 mg/kg BW (i.p.) once/week for 4 weeks. Groups III and IV were treated in the same way as the DOX group, left for one week without medication, and then injected with mesenchymal stromal cells (MSCs) or human placental extract (HPE) therapy in a single dose of 5 × 106 in 200 ml PRP/week or 40 µl placental extract for 4 weeks via the caudal vein. Group V rats were treated in the same way as the DOX group also, left for one week without medication, and then injected with MSC+HPE. A significant decrease in serum testosterone, FSH, and LH levels was observed in rats treated with DOX compared to the control group. A significant elevation was recorded in rats treated with DOX+MSC or DOX+HPE when compared with the DOX group only. Rats that were given MSC+HPE after DOX intoxication showed a significant increase in hormone levels when compared to rats treated with either MSC or HPE. Light and electron microscopic examinations revealed that DOX intoxication initiated degenerative and necrotic changes in seminiferous tubules associated with partial or complete cessation of spermatogenesis. These effects were reversed by the effect of MSC or HPE. Coadministration of MSC and HPE even showed further improvement. Finally, we can say that doxorubicin has a deleterious impact on rat testes; however, therapeutic effects can be induced through MSC and/or HPE administration.

Punica granatum and amygdalin extracts plus cobalamin combined with albendazole reduce larval burden and myositis in experimental trichinosis / Extratos de Punica granatum e amígdalina mais cobalamina combinado com albendazol reduzem a carga larvar e a miosite na triquinose experimental

Abstract Trichinellosis is a zoonosis results from eating raw or semi-cooked meat of infected animals. Medicinal plants have been used lately as alternatives and/or combined therapies to resolve some drawbacks of the current regimens. This work analyzed the effect of albendazole monotherapy on Trichinella spiralis experimental infection (group A), in comparison to P. granatum and amygdalin extracts +cobalamin (group B), plus its combination with albendazole (group C). The study revealed that the extracts alone or combined with albendazole had an inferior effect to albendazole monotherapy regarding number of adult worms (40.83 ±3.82, 18.67 ±1.86 and 16.83 ±2.32, respectively). However, their effect was more obvious in muscle phase combined with albendazole, achieving the lower number of larvae/mL tissue homogenate (22.33 ±3.27 in comparison to 39.67 ±2.58 achieved by albendazole monotherapy). The extracts exerted a significant immunomodulatory effect by reducing the local CD4+ expression in the intestine as well as in muscle phase (1.15 ±0.25 and 3.80 ±0.65 in comparison to 4.97 ±0.37 and 12.20 ±0.87 with albendazole monotherapy, respectively). So, these extracts improved the therapeutic efficacy of albendazole, specifically in muscle phase and counteracted the inflammatory reaction caused by albendazole monotherapy, thus extensively alleviating the resulting myositis.

Resumo Trichinellosis é uma zoonose resultante da ingestão de carne crua ou semicozida de animais infectados. As plantas medicinais têm sido usadas, ultimamente, como alternativas e/ou terapias combinadas, para resolver algumas desvantagens dos regimes atuais. Este trabalho analisou o efeito da monoterapia albendazole na infecção experimental por Trichinella spiralis (grupo A), em comparação com extratos de P. granatum e amígdalina +cobalamina (grupo B), além de sua combinação com albendazol (grupo C). O estudo revelou que os extratos sozinho ou combinado com albendazol teve efeito inferior à monoterapia albendazol em relação ao número de vermes adultos (40,83 ±3,82, 18,67 ±1,86 e 16,83 ±2,32, respectivamente). No entanto, seu efeito foi mais óbvio na fase muscular combinado com o albendazol, alcançando o menor número de larvas/mL homogeneizado de tecido (22,33 ±3,27 em comparação com 39,67 ±2,58 obtidos pela monoterapia albendazol). Os extratos exerceram um efeito imunomodulatório significativo, ao reduzir a expressão local CD4+ no intestino, bem como na fase muscular (1,15 ±0,25 e 3,80 ±0,65 em comparação com 4,97 ±0,37 e 12,20 ±0,87 com monoterapia albendazol, respectivamente). Assim, esses extratos melhoraram a eficácia terapêutica do albendazol, especificamente na fase muscular e neutralizaram a reação inflamatória causada pela monoterapia albendazol, aliviando extensivamente a miosite resultante.

Antiparasitic and immunomodulating effects of nitazoxanide, ivermectin and selenium on Cryptosporidium infection in diabetic mice / Efeitos antiparasitários e imunomodulantes da nitazoxanida, ivermectina e selênio sobre a infecção por Cryptosporidium em camundongos diabéticos

Abstract The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

Resumo O presente trabalho tem como objetivo investigar os efeitos anti-parasitários e imunomodulantes da nitazoxanida (NTZ) e ivermectina (IVC), isoladas ou em associação, e do selênio (SE), associado à NTZ ou à IVC, sobre a infecção por Cryptosporidium em camundongos diabéticos. Os resultados revelaram que a terapia combinada com NTZ e IVC resultou em maior redução de oocistos fecais, enquanto a NTZ isolada mostrou a menor redução de oocistos fecais (63%). Além disso, a associação do SE com a NTZ ou IVC resultou em redução do número de oocistos fecais de 63% para 71% e de 82% para 84%, respectivamente. Todos os tratamentos, com exceção da monoterapia com NTZ, mostraram uma melhora significativa nos índices relacionados à histopatologia intestinal. Os resultados da imuno-histoquímica mostraram reversão da razão celular CD4/CD8 T normal nos camundongos infectados não tratados, no entanto, após a terapia, houve retorno à razão celular CD4/CD8 T normal. O tratamento combinado (NTZ+ IVC) demonstrou o mais alto nível de expressão celular CD4 T. Em conclusão, a terapia combinada com NTZ e IVC mostrou efeitos anti-parasitários e imunoestimuladores notáveis, especificamente para a população CD4, que parecem ser promissores para o controle da criptosporidiose em indivíduos diabéticos.

Protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity.

Cisplatin is broadly used in the treatment of malignancies. However, the high incidence of nephrotoxicity following cisplatin use deters its clinical utility. Former studies have shown that the essential oils, obtained from Citrus limonia demonstrated significant anti-inflammatory and antioxidant effects. The aim of the current work was to evaluate the protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity. Thirty-two adult male mice were divided into four groups, eight mice each. The control group received distilled water, and the second group received a single intraperitoneal injection of cisplatin (20 mg/kg), while the third and fourth groups received cisplatin plus Citrus limonia oil at 100 or 200 mg/kg for 10 days, respectively. GC-MS analysis showed that the major components in Citrus limonia oil were D-limonene, 5-methyl-pentadecane, (n)-menthol, 3,7-dimethyl-(E)-2,6-octadienal, 3,7-dimethyl-2,6-octadienal, and nonadecane. Biochemical analysis showed that cisplatin intoxication was associated with significantly increased (p < 0.05) serum levels of urea and creatine and pro-inflammatory cytokines, as well as augmented renal tissue oxidative stress. Light microscopic examination showed loss of renal architecture, atrophied glomeruli, interstitial hemorrhage, dilated cortical tubules with cast formation, and excessive collagen production. Electron microscopic examination revealed compressed and karyorrhectic endothelial nuclei with chromatin condensation in the glomeruli, accumulation of mesangial matrix, and obliteration of glomerular blood capillaries. Co-administration of Citrus limonia oil attenuated these effects in renal histopathological, morphometric, and ultrastructural examinations, frequently in a dose-dependent manner. In conclusion, Citrus limonia oil can ameliorate the toxic effect of cisplatin on mice kidneys, probably through its antioxidant and anti-inflammatory effects.