New neuroprotective derivatives of cinnamic acid by biotransformation.

Microbial transformation is extensively utilized to generate new metabolites in bulk amounts with more specificity and improved activity. As cinnamic acid was reported to exhibit several important pharmacological properties, microbial transformation was used to obtain its new derivatives with enhanced biological activities. By manipulating the 2-stage fermentation protocol of biotransformation, five metabolites were produced from cinnamic acid. Two of them were new derivatives; N-propyl cinnamamide 2̲ and 2-methyl heptyl benzoate 3̲ produced by Alternaria alternata. The other 3 metabolites, p-hydroxy benzoic acid 4̲, cinnamyl alcohol 5̲ and methyl cinnamate 6̲, were produced by Rhodotorula rubra, Rhizopus species and Penicillium chrysogeneum, respectively. Cinnamic acid and its metabolites were evaluated for their cyclooxygenase (COX) and acetylcholinesterase (AChE) inhibitory activities. Protection against H2O2 and Aß1-42 induced-neurotoxicity in human neuroblastoma (SH-SY5Y) cells was also monitored. Metabolite 4̲ was more potent as a COX-2 inhibitor than the parent compound with an IC50 value of 1.85 ± 0.07 µM. Out of the tested compounds, only metabolite 2̲ showed AChE inhibitory activity with an IC50 value of 8.27 µM. These results were further correlated with an in silico study of the binding interactions of the active metabolites with the active sites of the studied enzymes. Metabolite 3̲ was more potent as a neuroprotective agent against H2O2 and Aß1-42 induced-neurotoxicity than catechin and epigallocatechin-3-gallate as positive controls. This study suggested the two new metabolites 2̲ and 3̲ along with metabolite 4̲ as potential leads for neurodegenerative diseases associated with cholinergic deficiency, neurotoxicity or neuroinflammation.

Evaluation of the Corneal Endothelium Following Cataract Surgery in Diabetic and Non-Diabetic Patients.

The aim of this study was to evaluate the influence of phacoemulsification cataract surgery on the state of the corneal endothelium in diabetic versus non-diabetic patients. We compared the corneal cell morphology in 48 diabetics with good glycemic control and 72 non-diabetic patients before and after uneventful phacoemulsification. Corneal cell density, central corneal thickness, and hexagonality were measured preoperatively and post-surgery (at 1 and 4 weeks) by specular microscopy. The effect of age, gender, axial length, and anterior chamber depth on the parameters of the corneal endothelium were evaluated. We noticed a drop in the endothelial density in both groups postoperatively: a mean endothelial cell loss of 472.7 ± 369.1 in the diabetic group was recorded versus 165.7 ± 214.6 mean loss in the non-diabetic group after the first week. A significant increase in central corneal thickness was also noticed in both groups one week after phacoemulsification, but no statistical significance after 4 weeks in the diabetic group. In terms of cell hexagonality, statistically significant differences were noticed after 4 weeks in both groups. Overall, a significant difference between diabetic and non-diabetic population was noticed in terms of corneal endothelial cell loss after uneventful phacoemulsification cataract surgery. Routine specular microscopy and HbA1c evaluation is recommended before cataract surgery, while intraoperative precautions and high monitorisation in terms of pacho power intensity and ultrasound energy, along with a proper application of the dispersive viscoelastic substances are essential to reduce the risk of endothelial damage.

Innovative challenge for the inhibition of hepatocellular carcinoma progression by combined targeting of HSP90 and STAT3/HIF-1α signaling.

Hepatocellular carcinoma (HCC) is the third foremost cause of cancer-related deaths. HCC has a very bad prognosis because it is asymptomatic in the early stages, resulting in a late diagnosis, and it is highly resistant to conventional chemotherapy. Such chemotherapies have been proven disappointing because they provide extremely low survival benefits. This study discloses that the STAT3/HIF-1α is an auspicious therapeutic attack site for conceivable repression of HCC development. A site that can be targeted by simultaneous administration of a STAT3 inhibitor in the context of HSP90 inhibition. 17-DMAG binds to HSP90 and constrains its function, resulting in the degradation of HSP90 client proteins HIF-1α and STAT3. Hypoxia recruits STAT3/HIF-1α complex within the VEGF promoter. Additionally, it was acknowledged that STAT3 is an essential mediator of VEGF transcription by direct binding to its promoter. Furthermore, it induces HIF-1α stability and enhances its transcriptional activity. Herein, we revealed that the combination therapy using 17-DMAG and nifuroxazide, a STAT3 inhibitor, repressed the diethylnitrosamine-induced alterations in the structure of the liver. This effect was mediated via decreasing the levels of the HSP90 client proteins HIF-1α and pSTAT3 resulting in the suppression of the STAT3/HIF-1α complex transcriptional activity. To conclude, 17-DMAG/NFXZD combination therapy-induced disruption in the STAT3/HIF-1α loop led to a potential antiangiogenic activity and showed apoptotic potential by inhibiting autophagy and inducing ROS/apoptosis signaling. Additionally, this combination therapy exhibited promising survival prolongation in mice with HCC. Consequently, the use of 17-DMAG/NFXZD renders an inspirational perspective in managing HCC. However, further investigations are compulsory.

Seminal calbindin 2 level in azoospermia and oligoasthenoteratozoospermia and its correlation with seminal and hormonal parameters.

OBJECTIVES: We aimed to assess seminal calbindin 2 (CALB 2) expression in men with different semen parameters as well as its correlation with reproductive hormones in azoospermic patients and different semen parameters in oligoasthenoteratozoospermic patients. CALB 2 is also known as calretinin and 29 kDa calbindin. MATERIALS AND METHODS: This prospective study was performed on 96 cases from the andrology outpatient clinic divided into 3 groups as follows: group 1 including 32 non obstructive azoospermic (NOA) patients, group 2 including 32 patients with oligoasthenoteratozoospermia (OAT), and Group 3 including normozoospermic individuals as controls. Semen analysis and estimation of seminal CALB 2 concentrations by enzyme linked immunosorbent assay (ELISA) technique were performed for all participants. Reproductive hormones were measured in nonobstructive NOA patients. RESULTS: The mean seminal CALB 2 level was higher in OAT patients compared to NOA patients and controls (7.8 ± 1.30 ng/ml, 7.3 ± 0.80 and 7.4 ± 1.0, respectively). Furthermore, the study had shown strong positive correlations between CALB 2 and sperm normal forms in controls and OAT patients. In contrast, there was no significant correlation between seminal CALB 2 and any of the reproductive hormones measured in NOA patients. CONCLUSIONS: Seminal CALB 2 may play a role in increasing the abnormal forms in OAT patients.

A case of triple vas deferens complaining of infertility: A challenging case report

There are multiple congenital structural abnormalities that affect male urogenital tract which could affect either the male external genitalia, internal genitalia or both. Congenital anomalies of the vas deferens may be unilateral or bilateral that could be complete or segmental and include (agenesis, atresia, duplication, ectopy or diverticulum). Anomalies of the vas deferens may be isolated or may be associated with other congenital anomalies especially in the male urogenital tract. These rare vas anomalies may be discovered during genital examination (either clinically or radiologically) or even accidentally during inguinal surgeries as in varicocelectomy, hernia repair, vasectomy or orchiopexy. We hereby reported the first case of triple vas deferens in a 35-year-old male that was felt on spermatic cord examination and confirmed by trans-rectal ultrasonography. Thus, proper evaluation should be made for the cases of multiple vas deferens to avoid the accidental injury during the operation and to exclude other associated congenital anomalies. (AU)

Hay múltiples anormalidades estructurales congénitas que afectan al tracto urogenital masculino y que pueden afectar a los genitales externos masculinos, a los genitales internos o a ambos. Las anomalías congénitas de los conductos deferentes pueden ser unilaterales o bilaterales, que pueden ser completas o segmentarias e incluyen: agenesia, atresia, duplicación, ectopia o divertículo. Las anomalías de los conductos deferentes pueden ser aisladas o estar asociadas con otras anomalías congénitas, especialmente en el tracto urogenital masculino. Estas raras anomalías de los conductos deferentes pueden descubrirse durante el examen genital (ya sea clínica o radiológicamente) o incluso accidentalmente durante cirugías inguinales, como en la varicocelectomía, la reparación de hernias, la vasectomía o la orquiopexia. Por la presente comunicamos el primer caso de triple conducto deferente en un varón de 35 años que fue sometido a palpación en el examen del cordón espermático y se confirmó mediante ecografía transrectal. Por lo tanto, debe hacerse una evaluación adecuada de los casos de conductos deferentes múltiples para evitar la lesión accidental durante la operación y excluir otras anomalías congénitas asociadas. (AU)

Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis.

Ulcerative colitis is an idiopathic disease that is widely incident worldwide. Canagliflozin, antidiabetic agent, exhibited significant anti-inflammatory effects in a variety of animal models. Additionally, hyaluronic acid is considered one of the key players in the tissue regeneration process. It has been proven to modulate inflammation and cellular migration, which are the main phases of wound healing. The combination of hyaluronic acid with chitosan in microsphere fabrication was anticipated to reveal a synergistic muco-adhesiveness potential with additional advantage of the chitosan penetration enhancing effect. The current study aimed to explore the potential of canagliflozin-loaded chitosan-hyaluronic acid microspheres intrarectal administration to mitigate acetic acid-induced colitis in rats. Colon tissues were examined for macroscopic and microscopic pathological changes. ELISA and qRT-PCR techniques were applied for the detection of cytokines involved in the AMPK/NF-κB/NLRP3 axis. Intrarectal administration of this formula alleviated colitis severity, which was reflected by the reduced DAI, MES, colonic weight/length ratio and histopathological scoring values. Interestingly, canagliflozin-loaded chitosan-hyaluronic acid microspheres significantly enhanced AMPK phosphorylation and depressed NF-κB and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and the inhibition of several inflammatory cytokines, including IL-1ß, and IL-18. Overall, the current study revealed that the protective effects of the formula against acetic acid-induced colitis are primarily mediated via augmenting AMPK phosphorylation and its consequences of NF-κB inactivation. Since canagliflozin is not associated with hypoglycemic effects, clinical application of canagliflozin-loaded chitosan-hyaluronic acid microspheres represent a novel therapeutic option for the treatment of patients with ulcerative colitis.

Ambroxol, a mucolytic agent, boosts HO-1, suppresses NF-κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF-κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti-inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200 mg/kg/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO-1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF-κB signaling and its consequent target pro-inflammatory mediators, IL-6 and TNF-α. In contrast, IL-10 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti-inflammatory, antioxidant, and antiapoptotic properties.

A case of triple vas deferens complaining of infertility: A challenging case report.

There are multiple congenital structural abnormalities that affect male urogenital tract which could affect either the male external genitalia, internal genitalia or both. Congenital anomalies of the vas deferens may be unilateral or bilateral that could be complete or segmental and include (agenesis, atresia, duplication, ectopy or diverticulum). Anomalies of the vas deferens may be isolated or may be associated with other congenital anomalies especially in the male urogenital tract. These rare vas anomalies may be discovered during genital examination (either clinically or radiologically) or even accidentally during inguinal surgeries as in varicocelectomy, hernia repair, vasectomy or orchiopexy. We hereby reported the first case of triple vas deferens in a 35-year-old male that was felt on spermatic cord examination and confirmed by trans-rectal ultrasonography. Thus, proper evaluation should be made for the cases of multiple vas deferens to avoid the accidental injury during the operation and to exclude other associated congenital anomalies.

Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis.

Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC.

Combining the HSP90 inhibitor TAS-116 with metformin effectively degrades the NLRP3 and attenuates inflammasome activation in rats: A new management paradigm for ulcerative colitis.

Ulcerative colitis (UC) is a prevalent type of inflammatory bowel diseases that may predispose patients to acquire colitis-related cancer if treatment was not effective. Despite the presence of an array of established treatment options, current modalities are not successful for a substanial number of patients. The activation of the NLRP3 inflammasome is critical in the development of inflammatory processes in the colon. Additionally, the regulation of NLRP3 via HSP90 inhibition is a potential target to treat UC. Moreover, during inflammation, autophagy allows the turnover of malfunctioning proteins and therefore stands as a viable strategy for inactivating NLRP3 inflammasomes and halting hyperinflammation. Herein, we evaluated the effect of autophagy induction using metformin in the context of HSP90 inhibition by TAS-116 in the dextran sodium sulfate (DSS)-induced UC in rats. We revealed that TAS-116-induced interruption of the protein complex containing HSP90 and NLRP3 might hamper and delay the start of the inflammatory cascade ensued by the NLRP3 inflammasome oligomerization. In such circumstances, the unprotected NLRP3 is subjected to autophagic degradation in an environment of metformin-promoted autophagic signaling. As a result, such dynamic synergy was efficient in combating colon damage and immune-cell infiltration. This was confirmed by the macroscopic and microscopic investigations. Further, biochemical analysis revealed subdued inflammation cascade and oxidative injury. Therefore, simultaneous administration of TAS-116 and metformin is a new management paradigm aimed at inducing malfunction in the NLRP3 followed by augmenting its autophagic degradation, respectively. However, further studies should be conducted to assess the reliability and consistency of this novel approach.

Empagliflozin adjunct with metformin for the inhibition of hepatocellular carcinoma progression: Emerging approach for new application.

Hepatocellular carcinoma (HCC) is on the rise worldwide, and its incidence in diabetic patients is two to three times that of non-diabetics. Current therapeutic options fail to provide considerable survival benefits to patients with HCC. There is a strong possibility that the FDA-approved antidiabetic combination of empagliflozin and metformin could show complementary effects to control HCC progression. However, their multitarget effects have not yet been studied on HCC development. Therefore, the present study aims to evaluate the antitumorigenic activity of this combination in non-diabetic mice with diethylnitrosamine-induced HCC. Empagliflozin/metformin combination prolonged survival and improved histological features of mice livers. Additionally, Empagliflozin/metformin showed anti-inflammatory potential and relieved oxidative stress. On the one hand these effects are likely attributed to the ability of metformin to inactivate NF-κB in an AMPK-dependent mechanism and on the other hand to the ability of the empagliflozin to inhibit the MAPKs, p38 and ERK1/2. Empagliflozin also showed a less robust effect on AMPK than that of metformin. Moreover, empagliflozin enhanced the autophagy inducing activity of metformin. Furthermore, empagliflozin/metformin exhibited increased apoptotic potential. Consequently, empagliflozin augmented the antitumorigenic function of metformin by exerting better control of angiogenesis, and metastasis. To conclude, our findings suggest empagliflozin as an ideal adjunct to metformin for the inhibition of HCC progression. In addition, since the incidence of hypoglycemia is minimal due to insulin-independent mechanism of action of both treatments, empagliflozin/metformin could be a promising therapeutic modality for the management of diabetic patients with HCC; and even non diabetic ones.

Benzo[a]pyrene immunogenetics and immune archetype reprogramming of lung.

Overexposure to carcinogenic precursor, benzo[a]pyrene [BaP], modulates the lung immune microenvironment. The present review seeks to elucidate novel pathways behind the tumor effect of BaP in the lungs, emphasizing immunomodulatory mediators and immune cells. In this review, BaP reprograms lung immune microenvironment through modulating transforming growth factor-beta (TGF-ß), programmed cell death 1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), Interleukin 12 (IL-12), indoleamine 2,3 dioxygenase (IDO), forkhead box protein P3 (FOXP3) and interferon-gamma (IFN-γ) levels. Moreover, BaP modulated lung immune cellular architecture such as dendritic cells, T cells, Tregs, macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs). All mentioned changes in immune architecture and mediators lead to the induction of lung cancer.

Blunting p38 MAPKα and ERK1/2 activities by empagliflozin enhances the antifibrotic effect of metformin and augments its AMPK-induced NF-κB inactivation in mice intoxicated with carbon tetrachloride.

AIM: Metformin and empagliflozin combined therapy may have complementary effects that go beyond the well-recognized targets of their monotherapy through AMPK activation. Therefore, the current study was designed to investigate for the first time the hepatoprotective effects of such combination therapy in the carbon tetrachloride (CCl4)-induced hepatic fibrosis model in mice. MATERIALS AND METHODS: Determination of liver enzymes and the liver content of oxidative stress parameters, and hydroxyproline were performed biochemically. ELISA was performed to measure PDGF-BB, TNF-α, TGF-ß, TIMP-1, AMPK, p-mTOR, NF-κB P65 binding activity, p38 MAPKα, JNK1/2 and ERK1/2. Real-time qPCR was conducted to determine Col1a1 and α-SMA. In addition, histopathological examination using H&E and Masson's trichrome stain were performed for determination of histopathological changes. KEY FINDINGS: Empagliflozin inhibited the activation of p38 MAPK and ERK1/2 and exhibited a weak AMPKα stimulation. On the other hand, metformin exerted a more robust stimulatory action on the AMPKα that was accompanied by a notable decrease in the NF-κB nuclear binding activity and a decline in the p-mTOR levels. Nevertheless, the effect of metformin on MAPK kinases was insignificant. Our results revealed that blunting p38 MAPKα and ERK1/2 activities by empagliflozin enhanced the antifibrotic effect of metformin and augmented its AMPK-induced NF-κB inactivation. SIGNIFICANCE: As diabetes is one of the most common risk factors for liver fibrosis, the use of antidiabetic drugs is expected to improve therapeutic outcome. Therefore, metformin/empagliflozin combined therapy could be promising in preventing hepatic inflammation and fibrosis via exhibiting complementary effects particularly in diabetic patients.

Telmisartan alleviates alcohol-induced liver injury by activation of PPAR-γ/ Nrf-2 crosstalk in mice.

Excessive consumption of alcohol may induce severe liver damage, in part via oxidative stress and inflammatory responses, which implicates these processes as potential therapeutic approaches. Prior literature has shown that Telmisartan (TEL) may provide protective effects, presumably mediated by its anti-oxidant and anti-inflammatory activities. The purpose of this study was to determine TEL's hepatoprotective effects and to identify its possible curative mechanisms in alcoholic liver disease. A mouse chronic alcohol plus binge feedings model was used in the current study for induction of alcoholic liver disease (ALD). Our results showed that TEL (10 mg/kg/day) has the ability to reduce serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). TEL also increased the activity of superoxide dismutase (SOD) and glutathione (GSH) with concomitant reduction of nitric oxide (NO) malonaldehyde (MDA) in the liver homogenate. Moreover, TEL downregulated nuclear factor kappa B (NF-κB) expression and decreased liver content of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). These anti-inflammatory and anti-oxidant activities were associated with a significant increase in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), peroxisome proliferator-activated receptors -γ (PPAR-γ), and heme oxygenase-1 (Hmox-1). In conclusion, TEL's hepatoprotective effects against ALD may be attributable to its anti-inflammatory and anti-oxidant activities which may be in part via the modulation of PPAR-γ/ Nrf-2/ NF-κB crosstalk.

AKT-AMPKα-mTOR-dependent HIF-1α Activation is a New Therapeutic Target for Cancer Treatment: A Novel Approach to Repositioning the Antidiabetic Drug Sitagliptin for the Management of Hepatocellular Carcinoma.

HIF-1α is a key factor promoting the development of hepatocellular carcinoma (HCC). As well, AKT-AMPKα-mTOR signaling is a promising target for cancer therapy. Yet, the AKT-AMPKα-mTOR-dependent activation of HIF-1α has not been studied in livers with HCC. In addition, the mechanisms underlying the potential antineoplastic effects of sitagliptin (STGPT), an antidiabetic agent, have not yet been elucidated. For that purpose, the N-nitrosodiethylamine (NDEA)-induced HCC mouse model was used in the present study using a dose of 100 mg/kg/week, i.p., for 8 weeks. NDEA-induced HCC mice received STGPT 20, 40, or 80 mg/kg starting on day 61 up to day 120. The present study revealed that STGPT inhibited HIF-1α activation via the interference with the AKT-AMPKα-mTOR axis and the interruption of IKKß, P38α, and ERK1/2 signals as well. Accordingly, STGPT prolonged the survival, restored the histological features and improved liver function. Additionally, STGPT inhibited angiogenesis, as revealed by a significant downregulation in the VEGF and mRNA expression of CD309 with concomitant inhibition of tissue invasion was evident by an increased ratio of TIMP-1/MMP-2. STGPT exhibited apoptotic stimulatory effect as indicated upon calculating the BCL-2/Bax ratio and by the gene expression of p53. The decrease in AFP and liver index calculation, gene expression of Ki-67 confirmed the antiproliferative activity of STGPT. The anti-inflammatory potential was revealed by the decreased TNF-α level and the downregulation of MCP-1 gene expression. Moreover, an antifibrotic potential was supported by lower levels of TGF-ß. These effects appear to be GLP1R-independent. The present study provides a potential basis for repurposing STGPT for the inhibition of HCC progression. Since STGPT is unlikely to cause hypoglycemia, it may be promising as monotherapy or adjuvant therapy to treat diabetic or even normoglycemic patients with HCC.

Combined Effects of Extracorporeal Shockwave Therapy and Integrated Neuromuscular Inhibition on Myofascial Trigger Points of Upper Trapezius: A Randomized Controlled Trial

Objective@#To investigate the combined effect of extracorporeal shockwave therapy (ESWT) and integrated neuromuscular inhibition (INI) on myofascial trigger points in the upper trapezius. @*Methods@#Sixty subjects aged 18–24 years old with active myofascial trigger points in the upper trapezius were studied. Participants were assigned randomly to either group A who received ESWT one session/week, group B who received INI three sessions/week, or group C who received ESWT in addition to INI. All groups completed 4 weeks of intervention. The following main outcome measures were evaluated at baseline and after 4 weeks of intervention: pain intensity, functional disability, pressure pain threshold (PPT), sympathetic skin response (SSR), and neuromuscular junction response (NMJR). @*Results@#Within-group analysis revealed a significant decline in visual analog scale (VAS), Arabic neck disability index (ANDI), and NMJR and incline in PPT and SSR latency post-intervention (p<0.001). Multiple comparison analysis showed a substantial difference between the groups, while the major changes favored group C (p<0.05). @*Conclusion@#Combined treatment with ESWT and INI for treating myofascial trigger points in the upper trapezius is more effective than using only one of the two approaches in terms of clinical, functional, and neurophysiological aspects.

Combined Effects of Extracorporeal Shockwave Therapy and Integrated Neuromuscular Inhibition on Myofascial Trigger Points of Upper Trapezius: A Randomized Controlled Trial

Objective@#To investigate the combined effect of extracorporeal shockwave therapy (ESWT) and integrated neuromuscular inhibition (INI) on myofascial trigger points in the upper trapezius. @*Methods@#Sixty subjects aged 18–24 years old with active myofascial trigger points in the upper trapezius were studied. Participants were assigned randomly to either group A who received ESWT one session/week, group B who received INI three sessions/week, or group C who received ESWT in addition to INI. All groups completed 4 weeks of intervention. The following main outcome measures were evaluated at baseline and after 4 weeks of intervention: pain intensity, functional disability, pressure pain threshold (PPT), sympathetic skin response (SSR), and neuromuscular junction response (NMJR). @*Results@#Within-group analysis revealed a significant decline in visual analog scale (VAS), Arabic neck disability index (ANDI), and NMJR and incline in PPT and SSR latency post-intervention (p<0.001). Multiple comparison analysis showed a substantial difference between the groups, while the major changes favored group C (p<0.05). @*Conclusion@#Combined treatment with ESWT and INI for treating myofascial trigger points in the upper trapezius is more effective than using only one of the two approaches in terms of clinical, functional, and neurophysiological aspects.

CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients.

BACKGROUND: Tacrolimus is an approved first-line immunosuppressive agent for kidney transplantations. Part of interindividual and interethnic differences in the response of patients to tacrolimus is attributed to polymorphisms at CYP3A5 metabolic enzyme. CYP3A5 gene expression status is associated with tacrolimus dose requirement in renal transplant recipients. MATERIALS AND METHODS: In this study, we determined the allelic frequency of CYP3A5*3 in 76 renal transplanted patients of Egyptian descent. Secondly, we evaluated the influence of the CYP3A5 gene variant on tacrolimus doses required for these patients as well on dose-adjusted tacrolimus trough-concentrations. RESULTS: The CYP3A5*3 variant was the most frequent allele detected at 85.53%. Additionally, our results showed that, mean tacrolimus daily requirements for heterozygous patients (CYP3A5*1/*3) were significantly higher compared to homozygous patients (CYP3A5*3/*3) during the first year after kidney transplantation. CONCLUSION: This is the first study in Egypt contributing to the individualization of tacrolimus dosing in Egyptian patients, informed by the CYP3A5 genotype.

Empagliflozin ameliorates ethanol-induced liver injury by modulating NF-κB/Nrf-2/PPAR-γ interplay in mice.

BACKGROUND: Excessive alcohol intake contributes to severe liver damage involving oxidative stress and inflammatory responses, which make them promising therapeutic targets. Previous studies have demonstrated that empagliflozin (EMPA) showed cardiovascular, renal, and cerebral benefits potentially mediated through its antioxidant and anti-inflammatory actions. AIMS: This experiment aimed to evaluate the hepatoprotective effect of EMPA on alcoholic liver disease (ALD) and the possible underlying mechanisms. MATERIALS AND METHODS: Serum biochemical parameters and the liver contents of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured. Real-time qPCR was conducted to determine the gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (Hmox-1). In addition, ELISA was performed to measure tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, Nrf-2, and PPAR-γ. Nuclear factor-kappa B (NF-κB) was detected by immunohistochemical staining using an anti-NF-κB p65 antibody. KEY FINDINGS: Our results revealed that the serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were significantly reduced by EMPA. EMPA also decreased the content of MDA and NO and increased the activities of SOD and GSH in liver homogenates. Moreover, EMPA inhibited the release of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, via the downregulation of NF-κB. These changes were associated with an improvement in histopathological deterioration. The protective effect of EMPA against oxidative stress and inflammation was associated with the upregulation of PPAR-γ, Nrf-2, and their target gene Hmox-1. SIGNIFICANCE: EMPA showed protective activities against ethanol-induced liver injury by suppressing inflammation and oxidative stress via modulation of the NF-κB/Nrf-2/PPAR-γ axis.

The Relationship of Close Marital Affairs to Healthy Women's Sexual Function: A Cross-Sectional Retrospective Study in Egypt.

INTRODUCTION: Some marriage-related factors may be associated with women's sexuality, but this topic has not been sufficiently investigated in developing countries. Indeed, these marital factors can be well planned and/or managed to achieve desirable outcomes; for instance, the legal age of marriage can be increased to 21 years. However, how this will reflect on women's sexuality should be clarified before any laws are changed. AIM: The purpose of this study was to investigate the associations of the age of marriage, number of children, educational level, duration of marriage, and aging with female sexual function among groups of Egyptian women. METHODS: We analyzed the recorded sociodemographic data and scores of the 19-item Female Sexual Function Index (FSFI) among 270 apparently healthy women aged 21-45 years. According to the studied variables, the data were divided into various subgroups. MAIN OUTCOME MEASURE: The sociodemographic data and scores of the FSFI. RESULTS: Marriage, before or after 21 years, was not correlated with sexual function. FSFI scores were significantly lower among women with ≥3 children and women who had been married for ≥10 years. FSFI scores were significantly lowest in women with the lowest educational level and those aged ≥40 years. CONCLUSION: It is important to ensure that people are equipped with accurate information. Sound knowledge can serve as the basis for informed decisions regarding the age of marriage and number of children desired. Furthermore, everyone, not just women, should be aware of the adverse sexual effects associated with long marriages and the age-related declines in sexual activity. Accordingly, women can achieve better sexual satisfaction. Hassanin AM, Kaddah AN, El-Amir MY. The Relationship of Close Marital Affairs to Healthy Women's Sexual Function: A Cross-Sectional Retrospective Study in Egypt. Sex Med 2019;7:498-504.