The diagnostic accuracy of intraoperative frozen section biopsy for diagnosis of sentinel lymph node metastasis in breast cancer patients: a meta-analysis

: Sentinel lymph node (SLN) sampling is important for evaluating the nodal stage of breast cancer when the axillary nodes are clinically free of metastasis. The intraoperative frozen section (IFS) of SLN is used for lymph node assessment. This meta-analysis aims to provide evidence about the diagnostic accuracy and the applicability of IFS of SLN in breast cancer patients. Data were collected by searching PubMed, Cochrane, Scopus, and Web of Science electronic databases for trials matching our eligibility criteria. The statistical analysis included the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and pooled studies' diagnostic odds ratio outcomes. The analyses were conducted using the Open Meta-analyst software. This meta-analysis pooled the results of 110 studies. The overall sensitivity of IFS for SLN metastasis was 74.7%; 95% CI [72.0, 77.2], P < 0.001. It was 31.4% 95% CI [25.2, 38.3], P < 0.001 for the micro-metastasis, and 90.2%; 95% CI [86.5, 93.0], P < 0.001 for the macro-metastasis. The overall specificity was 99.4%; 95% CI [99.2, 99.6], P < 0.001. The overall positive likelihood ratio was 121.4; 95% CI [87.9, 167.6], P < 0.001, and the overall negative likelihood ratio was 0.226; 95% CI [0.186, 0.274], P < 0.001. The overall diagnostic odds ratio of IFS for diagnosing SLN metastasis was 569.5; 95% CI [404.2, 802.4], P < 0.001. The intraoperative frozen section of SLN has good sensitivity for diagnosing breast cancer macro-metastasis. However, the sensitivity is low for micro-metastasis. The specificity is very satisfactory

MOLECULAR AND MORPHOLOGICAL IDENTIFICATION OF STREPTOMYCES SP. NRC-88 NOVA SPECIES AS β-LACTAMASE INHIBITOR FOR PHARMACEUTICAL APPLICATION

  Objective: Clavulanic acid (CA) is a vital agent in the treatment of bacterial infections since it is a potent inhibitor of an extensive variety of β-lactamase enzymes. Its production from Streptomyces strains is fact of expanding clinical significance. This study aimed to isolate and characterize a promising Streptomyces (S) species strain which produced an effective β-lactamase inhibitor.Methods: Streptomyces sp. NRC-88 was isolated from an Egyptian soil sample. The phenotypic and phylogenetic examinations of 16S rRNA gene were investigated. The active metabolite of this strain (CA) was determined by particular synergistic bioassay, spectrophotometric assay, recognized by thin layer chromatography, and structure of the CA affirmed by high-performance liquid chromatography (HPLC) method.Results: A phylogenetic examination of the 16S rRNA gene sequence of the NRC-88 strain consistent with conventional taxonomy was carried out, and confirmed that the strain NRC-88 was most similar to S. aburaviensis S-66 (99%). The active metabolite of this strain (CA) was determined by different methods and confirmed the structure of the CA by the HPLC method. It produced up to 87 mg/l in a specific CA production medium.Conclusion: A new species of Streptomyces sp. NRC-88 isolated and recognized by phenotypic and genotypic proof. This strain suggested the name, Streptomyces sp. NRC-88 (accession number KM014489). It was able to produce CA as the β-lactamase inhibitor

Ruta graveolens Protects Against Isoniazid/Rifampicin-Induced Nephrotoxicity through Modulation of Oxidative Stress and Inflammation

Background and Aim Drug-induced nephrotoxicity is a renal dyfunction that arises as a result of exposure to nephrotoxic drugs. Anti-tuberculosis therapy can cause nephrotoxicity and permanent kidney&nbsp; damage. The&nbsp; current&nbsp; study&nbsp; was&nbsp; designed&nbsp; to&nbsp; evaluate&nbsp; the&nbsp; possible&nbsp; protective&nbsp; effects&nbsp; of Ruta graveolens L. leaves extract against isoniazid/rifampicin-induced nephrotoxicity in rats.Methods:The experimental rats received isoniazid and rifampicin at dose level of 50 mg/kg, and 50 or 100 mg/kg/day Ruta graveolens leaves extract orally for 45 days.Results: Isoniazid/ rifampicin administration induced kidney injury evidenced by the histopathological alterations as well as significant (P&lt;0.001) increase in serum creatinine, urea and uric acid. soniazid/rifampicin-intoxicated rats exhibited a significant increase in serum tumor necrosis factor alpha (P&lt;0.001), and renal lipid peroxidation (P&lt;0.01) and nitric oxide (P&lt;0.001) levels. On the other hand, reduced glutathione level, and activity of superoxide dismutase and glutathione peroxidase were&nbsp; markedly&nbsp; (P&lt;0.001)&nbsp; declined&nbsp; in&nbsp; kidney&nbsp; of&nbsp; isoniazid/rifampicin-induced rats.Concomitant supplementation&nbsp; with&nbsp; either&nbsp; 50 or 100&nbsp; mg/kg&nbsp; dose&nbsp; of Ruta&nbsp; graveolens&nbsp; leaves&nbsp; extract&nbsp; prevented&nbsp; the isoniazid/rifampicin-induced biochemical and histopathological alterations. Conclusion:The present investigation confers new information on the protective mechanism of Ruta graveolens leaves extract on anti-tuberculosis therapy-induced nephrotoxicity.Ruta graveolens protects&nbsp; against isoniazid/rifampicin-induced renal injury through attattenuation of inflammation and oxidative stress, and potentiation of the antioxidant defense system.</p

ANTIDIABETIC AND INSULIN SENSITIZING EFFECTS OF PADINA PAVONIA AND TURBENARIA ORNATA IN STREPTOZOTOCIN/NICOTINAMIDE DIABETIC RATS

Objective:The current study was designed to investigate the hypoglycemic, hypolipidemic and insulin sensitizing effects of two marine brown algae, Padinapavoniaand Turbenariaornata.Materials and methods:Type 2 diabetes was induced by intraperitoneal injection of 120 mg/kg b.wt. nicotinamide 30 minutes before injection of 50 mg/kg b.wt. streptozotocin. Extracts of both Padinapavoniaand Turbenariaornata were orally and daily administered at a dose level of 100 mg/kg b.wt. for 21 days to diabetic rats. At the end of the experimental period, blood, pancreas and adipose tissue samples were taken for the subsequent studies.Results:Both Padinapavoniaand Turbenariaornata supplementation potentially ameliorated the elevated levels of glucose, AST, LDH and CK-MB and the lowered serum insulin levels of type 2 diabetic rats. Also, the tested algae increased the β-cell number in pancreata of diabetic rats. Both extracts were also found to alleviate the altered lipid profile and serum adiponectin level as well as the insulin resistance indices, HOMA-IR and QUICKI. In addition, both algae significantly upregulated adipose tissue adiponectin mRNA expression.Conclusion: These experimental findings demonstrated that both Padinapavoniaand Turbenariaornata exhibit antidiabetic effects in a rat model of type 2 diabetes by their insulinotropic and insulin sensitizing effects.Key Words: Adiponectin, insulin resistance, brown algae, diabetes

Consumption of Terpenoids-Rich Padina pavonia Extract Attenuates Hyperglycemia, Insulin Resistance and Oxidative Stress, and Upregulates PPARγ in a Rat Model of Type 2 Diabetes

Seaweeds are rich in structurally diverse bioactive compounds with promising therapeutic effects. This study aimed to isolate and identify terpenes from the brown alga Padina pavonia and to investigate its antidiabetic activity, pointing to the possible involvement of peroxisome proliferator-activated receptor (PPAR)&gamma;. Type 2 diabetes was induced by feeding rats a high fat diet (HFD) for 4 weeks followed by injection of 35 mg/kg streptozotocin (STZ). The diabetic rats received P. pavonia extract (PPE; 50, 100 and 200 mg/kg) for 4 weeks and samples were collected for analyses. HFD/STZ-induced rats showed hyperglycemia, dyslipidemia, impaired glucose tolerance, decreased insulin, and increased HbA1c and HOMA-IR. PPE ameliorated hyperglycemia and dyslipidemia, and improved glucose tolerance and insulin sensitivity in diabetic rats. Treatment with PPE increased hepatic hexokinase activity and glycogen, suppressed glucose-6-phosphatase, fructose-1,6-biphosphatase, and glycogen phosphorylase, and attenuated oxidative stress, inflammation, and liver injury and lipid infiltration in HFD/STZ-induced rats. In addition, PPE boosted antioxidants and upregulated PPAR&gamma; gene and protein expression in the liver of diabetic rats. Phytochemical investigation resulted in the isolation of six terpenes from PPE and in silico analysis revealed their binding affinity toward PPAR&gamma;. In conclusion, P. pavonia-derived terpenes attenuated hyperglycemia, dyslipidemia, oxidative stress, and inflammation, and improved insulin sensitivity and carbohydrate metabolism in type 2 diabetic rats. These beneficial effects are mediated via PPAR&gamma; activation. However, further studies to explore the exact mechanisms underlying the antidiabetic effect of PPE are recommended

The Combined Effect of Licorice Extract and Bone Marrow Mesenchymal Stem Cells on Cisplatin-Induced Hepatocellular Damage in Rats

Drug-induced liver damage is a life-threatening disorder, and one major form of it is the hepatotoxicity induced by the drug cisplatin. In folk medicine, Licorice (Glycyrrhiza glabra (is used for detoxification and is believed to be a potent antioxidant. Currently, the magically self-renewable potential of bone marrow mesenchymal stem cells (BM-MSCs) has prompted us to explore their hepatoregenerative capability. The impact of G. glabra extract (GGE) and BM-MSCs alone and, in combination, on protecting against hepatotoxicity was tested on cisplatin-induced liver injury in rats. Hepatic damage, as revealed by liver histopathology and increased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA), was elevated in rats by received 7 mg/kg of cisplatin intraperitoneally. The combination of GGE and BM-MSCs returned the enzyme levels to near the normal range. It also improved levels of liver superoxide dismutase (SOD) and glutathione (GSH) and reduced MDA levels. Additionally, it was found that when GGE and BM-MSCs were used together, they significantly downregulated caspase9 (Casp9), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and interleukin-1β (IL-1β), which are involved in severe proinflammatory and apoptotic signaling cascades in the liver. Moreover, combining GGE and BM-MSCs led to the normal result of hepatocytes in several examined liver histological sections. Therefore, our findings suggest that GGE may have protective effects against oxidative liver damage and the promising regenerative potential of BM-MSCs

Evaluation of Bifidobacteria and Lactobacillus Probiotics as Alternative Therapy for Salmonella typhimurium Infection in Broiler Chickens

Chicken Salmonella enterica serovars are enteric bacteria associated with massive public health risks and economic losses. There is a widespread antimicrobial resistance among S. enterica serotypes, and innovative solutions to antibiotic resistance are needed. We aimed to use probiotics to reduce antibiotic resistance and identify the major probiotic players that modify the early interactions between S. enterica and host cells. One-day-old cobb broiler chicks were challenged with S. typhimurium after oral inoculation with different probiotic strains for 3 days. The adherence of different probiotic strains to Caco-2 intestinal epithelial cells was studied in vitro. Lactobacillus (Lacticaseibacillus) casei ATTC334 and Bifidobacterium breve JCM1192 strains attached to Caco-2 cells stronger than B. infantis BL2416. L. casei ATTC334 and B. breve JCM1192 reduced S. typhimurium recovery from the cecal tonsils by competitive exclusion mechanism. Although B. infantis BL2416 bound poorly to Caco-2 epithelial cells, it reduced S. typhimurium recovery and increased IFN-&gamma; and TNF-&alpha; production. L. casei ATTC334, B. breve JCM1192 and B. infantis BL2416 improved body weight gain and the food conversion rate in S. typhimurium-infected broilers. B. longum Ncc2785 neither attached to epithelial cells nor induced IFN-&gamma; and TNF-&alpha; release and consequently did not prevent S. typhimurium colonization in broiler chickens. In conclusion, probiotics prevented the intestinal colonization of S. typhimurium in infected chickens by competitive exclusion or cytokine production mechanisms

Tongue microarchitecture and functional characterization of the lingual papillae in the desert hedgehog (Paraechinus aethiopicus)

The present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species

A Comprehensive Approach to Derivatization: Elemental Composition, Biochemical, and In Silico Studies of Metformin Derivatives Containing Copper and Zinc Complexes

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1–MCu9) and Zn II (MZn1–MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives’ biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski’s rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development

A Comprehensive Approach to Derivatization: Elemental Composition, Biochemical, and In Silico Studies of Metformin Derivatives Containing Copper and Zinc Complexes

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1&ndash;MCu9) and Zn II (MZn1&ndash;MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes &alpha;-amylase and &alpha;-glucosidase, and molecular simulations performed in Schr&ouml;dinger were used to assess the synthesized derivatives&rsquo; biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski&rsquo;s rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development