In silico and in vitro analyses to investigate the effects of vitamin C on VEGF protein.

Objectives: This study was conducted to evaluate the effects of vitamin C on apoptotic and proliferative genes in injured HepG2 cells. Methods: In silico analysis was performed using molecular docking of chemical compounds with vascular endothelial growth factor (VEGF). The different computational tools used were AutoDock Vina, BIOVIA DISCOVERY studio, and PyMOL. Drug likeness and toxicity were analyzed by SWISS ADMET. Cells that were 60-70% confluent were treated with different concentrations of hydrogen peroxide (H2O2) (100-2000 µM) and ascorbic acid (30, 60, 90 µg/mL). The MTT cell proliferation assay was performed to compare the proliferative potential of HepG2 cells treated with H2O2 or ascorbic acid with untreated HepG2 cells using 96-well plates. Results: The lowest binding energy of VEGF with vitamin C -5.2 kcal/mol and L-ascorbic acid-2 glycoside -4.7 kcal/mol was observed by in silico analysis. Vitamin C was selected because it exhibited a high interaction with VEGF and fulfilled Lipinski's rule, and had better oral viability and pharmacokinetics compared to L-ascorbic acid-2 glycoside. Cell viability assays showed that vitamin C had significant apoptotic effects (P < 0.0001). After treating HepG2 cells with ascorbic acid, reduced VEGF (angiogenesis) was observed as determined by apoptotic and proliferative gene expression. Ascorbic acid treatment of HepG2 cells led to downregulation of the proliferation markers, proliferating cell nuclear antigen, Ki67, and DNA topoisomerase II alpha. Increased apoptosis after treatment with vitamin C was observed due to upregulation of p53 and annexin V. Conclusion: The results of this study showed that vitamin C inhibited the growth of cancer cells, thus protecting HepG2 cells from oxidative stress. Vitamin C exhibited antiproliferative activity as observed in silico and in vitro, as well as by the inhibited expression of genes involved in protein synthesis.

Aspongopus chinensis ach-miR-276a-3p induces breast cancer cell cycle arrest by targeting APPL2 to regulate the CDK2-Rb-E2F1 signaling pathway.

Breast cancer, the most common cancer, presents a significant challenge to the health and longevity of women. Aspongopus chinensis Dallas is an insect with known anti-breast cancer properties. However, the anti-breast cancer effects and underlying mechanisms have not been elucidated. Exogenous microRNAs (miRNAs), which are derived from plants and animals, have been revealed to have notable capacities for controlling the proliferation of cancerous cells. To elucidate the inhibitory effects of miRNAs derived from A. chinensis and the regulatory mechanism involved in the growth of breast cancer cells, miRNA sequencing was initially employed to screen for miRNAs both in A. chinensis hemolymph and decoction and in mouse serum and tumor tissue after decoction gavage. Subsequently, the experiments were performed to assess the suppressive effect of ach-miR-276a-3p, the miRNA screened out from a previous study, on the proliferation of MDA-MB-231 and MDA-MB-468 breast cancer cell lines in vitro and in vivo. Finally, the regulatory mechanism of ach-miR-276a-3p in MDA-MB-231 and MDA-MB-468 breast cancer cells was elucidated. The results demonstrated that ach-miR-276a-3p notably inhibited breast cancer cell proliferation, migration, colony formation, and invasion and induced cell cycle arrest at the G0/G1 phase. Moreover, the ach-miR-276a-3p mimics significantly reduced the tumor volume and weight in xenograft tumor mice. Furthermore, ach-miR-276a-3p could induce cell cycle arrest by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway. In summary, ach-miR-276a-3p, derived from A. chinensis, has anti-breast cancer activity by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway and can serve as a promising candidate anticancer agent.

Aspongopus chinensis Dallas induces pro-apoptotic and cell cycle arresting effects in hepatocellular carcinoma cells by modulating miRNA and mRNA expression.

Aspongopus chinensis Dallas is a traditional Chinese medicinal insect with several anticancer properties can inhibit cancer cell growth, by inhibiting cell division, autophagy and cell cycle. However, the precise therapeutics effects and mechanisms of this insect on liver cancer are still unknown. This study examined the inhibitory influence of A. chinensis on the proliferation of hepatocellular carcinoma (HCC) cells and explore the underlying mechanism using high-throughput sequencing. The results showed that A. chinensis substantially reduced the viability of Hep G2 cells. A total of 33 miRNAs were found to be upregulated, while 43 miRNAs were downregulated. Additionally, 754 mRNAs were upregulated and 863 mRNAs were downregulated. Significant enrichment of differentially expressed genes was observed in signaling pathways related to tumor cell growth, cell cycle regulation, and apoptosis. Differentially expressed miRNAs exhibited a targeting relationship with various target genes, including ARC, HSPA6, C11orf86, and others. Hence, cell cycle and apoptosis were identified by flow cytometry. These findings indicate that A. chinensis impeded cell cycle advancement, halted the cell cycle in the G0/G1 and S stages, and stimulated apoptosis. Finally, mouse experiments confirmed that A. chinensis significantly inhibits tumor growth in vivo. Therefore, our findings indicate that A. chinensis has a notable suppressive impact on the proliferation of HCC cells. The potential mechanism of action could involve the regulation of mRNA expression via miRNA, ultimately leading to cell cycle arrest and apoptosis. The results offer a scientific foundation for the advancement and application of A. chinensis in the management of HCC.

Human epidermal growth receptor polymorphisms (HER1-rs11543848 and HER2-rs1136201) exhibited significant association with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan.

Background and Aims: Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1-rs11543848 and HER2-rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1-rs11543848 and HER2-rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods: A total of 314 women including 164 breast cancer patients and 150 age and gender-matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra-ARMS-PCR for genotyping and gel electrophoresis. Results: Our results indicated that HER1-rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258-5.6756, p = 0.0833). Similarly, the HER2-rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876-6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p < 0.005) with family history, metastasis, stage, luminal B, and TNBC. Conclusion: In conclusion, HER1-rs11543848 and HER2-rs1136201 polymorphisms are significantly associated with the higher risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. These findings advocate for further exploration with larger datasets, offering promising avenues for personalized approaches in breast cancer research and potentially enhancing clinical practices for better risk assessment and targeted management strategies.

Benzimidazole Derivative (N-{4-[2-(4-Methoxyphenyl)-1H-Benzimidazole-1-Sulfonyl] Phenyl} Acetamide) Ameliorates Methotrexate-Induced Intestinal Mucositis by Suppressing Oxidative Stress and Inflammatory Markers in Mice.

Methotrexate (MTX)-induced intestinal mucositis (IM) is a common side effect in cancer treatment that impairs the immune system and gut microbes, resulting in loss of mucosal integrity and gut barrier dysfunction. The quality of life and outcomes of treatment are compromised by IM. The present study was designed to investigate the mucoprotective potential of the benzimidazole derivative N-{4-[2-(4-methoxyphenyl)-1H-benzimidazole-1-sulfonyl] phenyl} acetamide (B8) on MTX-induced IM in mice. IM was induced by a single dose of MTX in mice and assessed by physical manifestations as well as biochemical, oxidative, histological, and inflammatory parameters. B8 (1, 3, 9 mg/kg) significantly reduced diarrhea score, mitigated weight loss, increased feed intake and, survival rate in a dose-dependent manner. Notably, B8 exhibited a mucoprotective effect evident through the mitigation of villus atrophy, crypt hypoplasia, diminished crypt mitotic figures, mucin depletion, and oxidative stress markers (GSH, SOD, MDA, and catalase concentration). Gene expression analysis revealed that B8 downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), IL-1ß, and nuclear factor-κB (NF-κB) and concurrently upregulated IL-10 expression in contrast to the MTX group. Further, B8 significantly improved the luminal microflora profile by augmenting the growth of Lactobacillus spp. and reducing the number of pathogenic bacteria (E. coli). Additionally, the enzyme-linked immunoassay showed that B8 decreased the levels of pro-inflammatory cytokines. Our findings suggest that B8 had mucoprotective effects against MTX-induced IM and could be used as an adjunct in chemotherapy to deter this side effect.

RETRACTED: Khan et al. Poly (N-vinylcaprolactam-grafted-sodium alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation. Pharmaceutics 2022, 14, 1050.

The journal retracts the article, "Poly (N-vinylcaprolactam-grafted-sodium alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hy-drogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation" [...].

Assessment of HER1 (rs11543848) and HER2 (rs1136201) polymorphism and their association with colorectal cancer susceptibility in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region. METHODS: In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR. RESULTS: Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352). CONCLUSION: In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results.

Identification, Genome Sequencing, and Characterizations of Helicobacter pylori Sourced from Pakistan.

The stomach's colonization by Helicobacter pylori (H. pylori) results in gastritis, ulcers, and stomach cancer. Frequently, pain is treated with medication, but resistant H. pylori infections are not. Therefore, it is important to find pharmacological targets and improved treatments for resistant H. pylori strains. The aim of the current study was sampling, identification, drug susceptibility testing following genome sequencing and comparative genome-wide analysis of selected H. pylori strains from Pakistan with three representative strains for virulence and drug-resistant characteristics. Based on culture, biochemistry, and molecular biology, 84 strains of H. pylori were identified, which made up 47% of the enrolled cases. Among all H. pylori strains, the highest resistance was reported for metronidazole with 82 H. pylori strains (98%), followed by clarithromycin with 62 resistant strains (74%). Among metronidazole-resistant strains, 38 strains (46%) were also resistant to clarithromycin, contributing 61% of clarithromycin resistant cases. Two strains, HPA1 and HPA2, isolated from 'gastritis' and 'gastric ulcer' patients, respectively, were further processed for WGS. The draft genome sequences of H. pylori strains HPA1 and HPA2 encode 1.66 Mbp and 1.67 Mbp genome size, 24 and 4 contiguous DNA sequences, and 1650 and 1625 coding sequences, respectively. Both the genomes showed greater than 90% similarity with the reference strain H. pylori ATCC 43504/PMSS1. The antibiotic-resistant genes were identified among all the strains with overall similarity above 95%, with minor differences in the sequence similarity. Using the virulent gene data obtained from the Virulence Factor Database, 75 to 85 virulent genes were identified in the five genome assemblies with various key genes such as cytolethal distending toxin (cdt), type IV secretion system, cag PAI, plasticity region, cell-motility- and flagellar-associated genes, neutrophil-activating protein (HP-NAP), T4SS effector cytotoxin-associated gene A (cagA), and urease-associated genes ureA and ureB, etc. Sequence similarity between the virulence factors found in this study and reference genes was at least 90%. In summary, the results of our study showed the relationship between clinical results and specific H. pylori strains' (HPA1 and HPA2) genetics such as antibiotic resistance and specific virulence factors. These findings provide valued understanding of the epidemiology of H. pylori-associated diseases. Moreover, identification and genomics analysis have provided insights into the epidemiology, genetic diversity, pathogenicity, and potential drug resistance genes of H. pylori strains, offering a foundation for developing more targeted and effective medical interventions, including anti-virulent medications.

Lung Tumor Image Segmentation from Computer Tomography Images Using MobileNetV2 and Transfer Learning.

BACKGROUND: Lung cancer is one of the most fatal cancers worldwide, and malignant tumors are characterized by the growth of abnormal cells in the tissues of lungs. Usually, symptoms of lung cancer do not appear until it is already at an advanced stage. The proper segmentation of cancerous lesions in CT images is the primary method of detection towards achieving a completely automated diagnostic system. METHOD: In this work, we developed an improved hybrid neural network via the fusion of two architectures, MobileNetV2 and UNET, for the semantic segmentation of malignant lung tumors from CT images. The transfer learning technique was employed and the pre-trained MobileNetV2 was utilized as an encoder of a conventional UNET model for feature extraction. The proposed network is an efficient segmentation approach that performs lightweight filtering to reduce computation and pointwise convolution for building more features. Skip connections were established with the Relu activation function for improving model convergence to connect the encoder layers of MobileNetv2 to decoder layers in UNET that allow the concatenation of feature maps with different resolutions from the encoder to decoder. Furthermore, the model was trained and fine-tuned on the training dataset acquired from the Medical Segmentation Decathlon (MSD) 2018 Challenge. RESULTS: The proposed network was tested and evaluated on 25% of the dataset obtained from the MSD, and it achieved a dice score of 0.8793, recall of 0.8602 and precision of 0.93. It is pertinent to mention that our technique outperforms the current available networks, which have several phases of training and testing.

Significant association of BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Single nucleotide polymorphism (SNPs) in BRCA1, BRCA2 and TP53 has been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan. METHODS: This study, consisting 140 breast cancer patients and 80 gender and age matched healthy controls were subjected to confirm BRCA1, BRCA2 and TP53 polymorphism. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using T-ARMS-PCR protocol. RESULTS: Our data indicated that BRCA1, BRCA2, and TP53 selected SNPs risk allele and risk allele containing genotypes displayed significant association (p < 0.05) with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. CONCLUSION: All the three selected SNPs of BRCA1, BRCA2 and TP53 showed significant association with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

TME-targeted approaches of brain metastases and its clinical therapeutic evidence.

The tumor microenvironment (TME), which includes both cellular and non-cellular elements, is now recognized as one of the major regulators of the development of primary tumors, the metastasis of which occurs to specific organs, and the response to therapy. Development of immunotherapy and targeted therapies have increased knowledge of cancer-related inflammation Since the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) limit immune cells from entering from the periphery, it has long been considered an immunological refuge. Thus, tumor cells that make their way "to the brain were believed to be protected from the body's normal mechanisms of monitoring and eliminating them. In this process, the microenvironment and tumor cells at different stages interact and depend on each other to form the basis of the evolution of tumor brain metastases. This paper focuses on the pathogenesis, microenvironmental changes, and new treatment methods of different types of brain metastases. Through the systematic review and summary from macro to micro, the occurrence and development rules and key driving factors of the disease are revealed, and the clinical precision medicine of brain metastases is comprehensively promoted. Recent research has shed light on the potential of TME-targeted and potential treatments for treating Brain metastases, and we'll use that knowledge to discuss the advantages and disadvantages of these approaches.

Isolation and screening of chromium resistant bacteria from industrial waste for bioremediation purposes / Isolamento e triagem de bactérias resistentes ao cromo de resíduos industriais para fins de biorremediação

Abstract Chromium (VI) a highly toxic metal, a major constituent of industrial waste. It is continuously release in soil and water, causes environmental and health related issues, which is increasing public concern in developing countries like Pakistan. The basic aim of this study was isolation and screening of chromium resistant bacteria from industrial waste collected from Korangi and Lyari, Karachi (24˚52ʹ46.0ʺN 66˚59ʹ25.7ʺE and 24˚48ʹ37.5ʺN 67˚06ʹ52.6ʺE). Among total of 53 isolated strains, seven bacterial strains were selected through selective enrichment and identified on the basis of morphological and biochemical characteristics. These strains were designated as S11, S13, S17, S18, S30, S35 and S48, resistance was determined against varying concentrations of chromium (100-1500 mg/l). Two bacterial strains S35 and S48 showed maximum resistance to chromium (1600 mg/l). Bacterial strains S35 and S48 were identified through 16S rRNA sequence and showed 99% similarity to Bacillus paranthracis and Bacillus paramycoides. Furthermore, growth condition including temperature and pH were optimized for both bacterial strains, showed maximum growth at temperature 30ºC and at optimum pH 7.5 and 6.5 respectively. It is concluded that indigenous bacterial strains isolated from metal contaminated industrial effluent use their innate ability to transform toxic heavy metals to less or nontoxic form and can offer an effective tool for monitoring heavy metal contamination in the environment.

Resumo O cromo (VI), metal altamente tóxico, é um dos principais constituintes dos resíduos industriais. É liberado no solo e na água, causa problemas ambientais e de saúde de crescente preocupação pública em países em desenvolvimento como o Paquistão. O objetivo básico deste estudo foi o isolamento e a triagem de bactérias resistentes ao cromo de resíduos industriais coletados em Korangi e Lyari, Karachi (24˚52'46,0"N 66˚59'25,7"E e 24˚48'37,5"N 67˚06'52,6"E). Do total de 53 cepas isoladas, sete cepas bacterianas foram selecionadas por enriquecimento seletivo e identificadas com base em características morfológicas e bioquímicas. Essas cepas foram designadas como S11, S13, S17, S18, S30, S35 e S48, apresentaram alta resistência aos metais contra concentrações variáveis (100-1500 mg / l) de cromo. Já as cepas S35 e S48 foram identificadas por meio da sequência 16S rRNA e apresentaram 99% de similaridade com Bacillus paranthracis e Bacillus paramycoides. Além disso, as condições de crescimento incluindo temperatura e pH foram otimizadas e ambas as cepas bacterianas apresentaram crescimento máximo na temperatura de 30 ºC, enquanto seu pH ótimo foi observado em 7,5 e 6,5, respectivamente. Conclui-se que o potencial de resistência dessas bactérias resistentes ao cromo pode ser efetivamente utilizado na remoção de cromo de efluentes industriais contaminados. Técnicas de base biológica usando bactérias ajudarão a fornecer métodos mais baratos e ecológicos de remoção, recuperação e desintoxicação de cromo.

Isolation and screening of chromium resistant bacteria from industrial waste for bioremediation purposes

Abstract Chromium (VI) a highly toxic metal, a major constituent of industrial waste. It is continuously release in soil and water, causes environmental and health related issues, which is increasing public concern in developing countries like Pakistan. The basic aim of this study was isolation and screening of chromium resistant bacteria from industrial waste collected from Korangi and Lyari, Karachi (245246.0N 665925.7E and 244837.5N 670652.6E). Among total of 53 isolated strains, seven bacterial strains were selected through selective enrichment and identified on the basis of morphological and biochemical characteristics. These strains were designated as S11, S13, S17, S18, S30, S35 and S48, resistance was determined against varying concentrations of chromium (100-1500 mg/l). Two bacterial strains S35 and S48 showed maximum resistance to chromium (1600 mg/l). Bacterial strains S35 and S48 were identified through 16S rRNA sequence and showed 99% similarity to Bacillus paranthracis and Bacillus paramycoides. Furthermore, growth condition including temperature and pH were optimized for both bacterial strains, showed maximum growth at temperature 30ºC and at optimum pH 7.5 and 6.5 respectively. It is concluded that indigenous bacterial strains isolated from metal contaminated industrial effluent use their innate ability to transform toxic heavy metals to less or nontoxic form and can offer an effective tool for monitoring heavy metal contamination in the environment.

Resumo O cromo (VI), metal altamente tóxico, é um dos principais constituintes dos resíduos industriais. É liberado no solo e na água, causa problemas ambientais e de saúde de crescente preocupação pública em países em desenvolvimento como o Paquistão. O objetivo básico deste estudo foi o isolamento e a triagem de bactérias resistentes ao cromo de resíduos industriais coletados em Korangi e Lyari, Karachi (245246,0N 665925,7E e 244837,5N 670652,6E). Do total de 53 cepas isoladas, sete cepas bacterianas foram selecionadas por enriquecimento seletivo e identificadas com base em características morfológicas e bioquímicas. Essas cepas foram designadas como S11, S13, S17, S18, S30, S35 e S48, apresentaram alta resistência aos metais contra concentrações variáveis (100-1500 mg / l) de cromo. Já as cepas S35 e S48 foram identificadas por meio da sequência 16S rRNA e apresentaram 99% de similaridade com Bacillus paranthracis e Bacillus paramycoides. Além disso, as condições de crescimento incluindo temperatura e pH foram otimizadas e ambas as cepas bacterianas apresentaram crescimento máximo na temperatura de 30 ºC, enquanto seu pH ótimo foi observado em 7,5 e 6,5, respectivamente. Conclui-se que o potencial de resistência dessas bactérias resistentes ao cromo pode ser efetivamente utilizado na remoção de cromo de efluentes industriais contaminados. Técnicas de base biológica usando bactérias ajudarão a fornecer métodos mais baratos e ecológicos de remoção, recuperação e desintoxicação de cromo.

Isolation and screening of chromium resistant bacteria from industrial waste for bioremediation purposes / Isolamento e triagem de bactérias resistentes ao cromo de resíduos industriais para fins de biorremediação

Chromium (VI) a highly toxic metal, a major constituent of industrial waste. It is continuously release in soil and water, causes environmental and health related issues, which is increasing public concern in developing countries like Pakistan. The basic aim of this study was isolation and screening of chromium resistant bacteria from industrial waste collected from Korangi and Lyari, Karachi (24˚52ʹ46.0ʺN 66˚59ʹ25.7ʺE and 24˚48ʹ37.5ʺN 67˚06ʹ52.6ʺE). Among total of 53 isolated strains, seven bacterial strains were selected through selective enrichment and identified on the basis of morphological and biochemical characteristics. These strains were designated as S11, S13, S17, S18, S30, S35 and S48, resistance was determined against varying concentrations of chromium (100-1500 mg/l). Two bacterial strains S35 and S48 showed maximum resistance to chromium (1600 mg/l). Bacterial strains S35 and S48 were identified through 16S rRNA sequence and showed 99% similarity to Bacillus paranthracis and Bacillus paramycoides. Furthermore, growth condition including temperature and pH were optimized for both bacterial strains, showed maximum growth at temperature 30ºC and at optimum pH 7.5 and 6.5 respectively. It is concluded that indigenous bacterial strains isolated from metal contaminated industrial effluent use their innate ability to transform toxic heavy metals to less or nontoxic form and can offer an effective tool for monitoring heavy metal contamination in the environment.

O cromo (VI), metal altamente tóxico, é um dos principais constituintes dos resíduos industriais. É liberado no solo e na água, causa problemas ambientais e de saúde de crescente preocupação pública em países em desenvolvimento como o Paquistão. O objetivo básico deste estudo foi o isolamento e a triagem de bactérias resistentes ao cromo de resíduos industriais coletados em Korangi e Lyari, Karachi (24˚52’46,0”N 66˚59’25,7”E e 24˚48’37,5”N 67˚06’52,6”E). Do total de 53 cepas isoladas, sete cepas bacterianas foram selecionadas por enriquecimento seletivo e identificadas com base em características morfológicas e bioquímicas. Essas cepas foram designadas como S11, S13, S17, S18, S30, S35 e S48, apresentaram alta resistência aos metais contra concentrações variáveis (100-1500 mg / l) de cromo. Já as cepas S35 e S48 foram identificadas por meio da sequência 16S rRNA e apresentaram 99% de similaridade com Bacillus paranthracis e Bacillus paramycoides. Além disso, as condições de crescimento incluindo temperatura e pH foram otimizadas e ambas as cepas bacterianas apresentaram crescimento máximo na temperatura de 30ºC, enquanto seu pH ótimo foi observado em 7,5 e 6,5, respectivamente. Conclui-se que o potencial de resistência dessas bactérias resistentes ao cromo pode ser efetivamente utilizado na remoção de cromo de efluentes industriais contaminados. Técnicas de base biológica usando bactérias ajudarão a fornecer métodos mais baratos e ecológicos de remoção, recuperação e desintoxicação de cromo.

Lightweight Deep Learning Classification Model for Identifying Low-Resolution CT Images of Lung Cancer.

With an astounding five million fatal cases every year, lung cancer is among the leading causes of mortality worldwide for both men and women. The diagnosis of lung illnesses can benefit from the information a computed tomography (CT) scan can offer. The major goals of this study are to diagnose lung cancer and its seriousness and to identify malignant lung nodules from the provided input lung picture. This paper applies unique deep learning techniques to identify the exact location of the malignant lung nodules. Using a DenseNet model, mixed ground glass is analyzed in low-dose, low-resolution CT scan images of nodules (mGGNs) with a slice thickness of 5 mm in this study. This was done to categorize and identify many histological subtypes of lung cancer. Low-resolution CT scans are used to pathologically classify invasive adenocarcinoma (IAC) and minimally invasive adenocarcinoma (MIA). 105 low-resolution CT images with 5 mm thick slices from 105 patients at Lishui Central Hospital were selected. To detect and distinguish, IAC and MIA, extend and enhance deep learning two- and three-dimensional DenseNet models are used. The two-dimensional DenseNet model was shown to perform much better than the three-dimensional DenseNet model in terms of classification accuracy (76.67%), sensitivity (63.3%), specificity (100%), and area under the receiver operating characteristic curve (0.88). Finding the histological subtypes of persons with lung cancer should aid doctors in making a more precise diagnosis, even if the image quality is not outstanding.

Sodium alginate/N-(Vinylcaprolactam) based supramolecular self-assembled subcutaneously administered in situ formed gels depot of 5-fluorouracil: Rheological analysis, in vitro cytotoxic potential, in vivo bioavailability and safety evaluation.

In current study, novel in situ formed injectable self-assembled thermoreversible depot gels based on N-(Vinylcaprolactam) were synthesized with a carbohydrate polymer i.e. sodium alginate in aqueous solution using cold method. The prepared gels preparations were intended to be utilized as 5-FU delivery depot after injectable administration through subcutaneous route. The structural characterization of self-assembled gels samples were studied through FTIR. The thermal properties of newly formed gels complexes were investigated by DSC and TGA. While the morphology of gels were assessed through SEM. The tunable gelation temperatures and phase transition of optimized formulations were confirmed by tube inverting, rheology determination and optical transmittance test. Thermo and pH response was evaluated at different temperatures and in various acidic and basic buffer solutions. In vitro release experiments were conducted using Franz diffusion system to monitor the controlled delivery fashion of gels matrices. Results concluded that depot gels exhibit controlled delivery fashion with maximum release at pH 7.4 and 37 ± 2 °C. The biocompatible nature of blank gels samples was assessed by MTT assay against Vero cell lines and was found safe. While killing ability of 5-FU encapsulated gels was evaluated against HeLa (19 ± 0.22 µg/ml; 23 ± 0.55 µg/ml) and MCF-7 (21 ± 0.06 µg/ml and 22 ± 0.34 µg/ml) cancer cell lines and were found effective to kill cancer cells. Histopathological study showed that gels depot is safe with no harmful effects on major organs. The in vivo bioavailability in rabbits showed controlled release (Cmax, 4465.78 ± 1.99 ng/ml) in comparison to free drug (Cmax, 4883.73 ± 3.32 ng/ml) administration after subcutaneous injection.

Poly (N-Vinylcaprolactam-Grafted-Sodium Alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation.

This study was aimed to develop novel in situ forming gels based on N-vinylcaprolactam, sodium alginate, and N,N-methylenebisacrylamide. The in situ Poly (NVRCL-g-NaAlg) gels were developed using the cold and free radical polymerization method. The structure formation, thermal stability, and porous nature of gels was confirmed by FTIR, NMR, DSC, TGA, and SEM. The tunable gelation temperature was evaluated by tube titling and rheological analysis. Optical transmittance showed that all formulations demonstrated phase transition around 33 °C. The swelling and release profile showed that gels offered maximum swelling and controlled 5-FU release at 25 °C and pH (7.4), owing to a relaxed state. Porosity and mesh size showed an effect on swelling and drug release. The in vitro degradation profile demonstrated a controlled degradation rate. An MTT assay confirmed that formulations are safe tested against Vero cells. In vitro cytotoxicity showed that 5-FU loaded gels have controlled cytotoxic potential against HeLa and MCF-7 cells (IC50 = 39.91 µg/mL and 46.82 µg/mL) compared to free 5-FU (IC50 = 50.52 µg/mL and 53.58 µg/mL). Histopathological study demonstrated no harmful effects of gels on major organs. The in vivo bioavailability in rabbits showed a controlled release in gel form (Cmax, 1433.59 ± 45.09 ng/mL) compared to a free drug (Cmax, 2263.31 ± 13.36 ng/mL) after the subcutaneous injection.

Effective Image Processing and Segmentation-Based Machine Learning Techniques for Diagnosis of Breast Cancer.

Breast cancer is the second leading cause of death among women, behind only heart disease. However, despite the high incidence and mortality rates associated with breast cancer, it is still unclear as to what is responsible for its development in the first place. The prevention of breast cancer is not possible with any of the current available methods. Patients who are diagnosed and treated for breast cancer at an early stage have a better chance of having a successful treatment and recovery. In the field of breast cancer detection, digital mammography is widely acknowledged to be a highly effective method of detecting the disease early on. We may be able to improve early detection of breast cancer with the use of image processing techniques, thereby boosting our chances of survival and treatment success. This article discusses a breast cancer image processing and machine learning framework that was developed. The input data set for this framework is a sequence of mammography images, which are used as input data. The CLAHE approach is then utilized to improve the overall quality of the photographs by means of image processing. It is called contrast restricted adaptive histogram equalization (CLAHE), and it is an improvement on the original histogram equalization technique. This aids in the removal of noise from photographs while simultaneously improving picture quality. The segmentation of images is the next step in the framework's development. An image is divided into distinct portions at this point because the pixels are labeled at this step. This assists in the identification of objects and the delineation of boundaries. To categorize these preprocessed images, techniques such as fuzzy SVM, Bayesian classifier, and random forest are employed, among others.

Synergy in penicillin, cephalosporin, amphenicols, and aminoglycoside against MDR S. aureus isolated from Camel milk

Abstract This study investigated the synergy testing of penicillin, cephalosporin, amphenicols, and aminoglycoside in the camel milk (n=768 samples), subsequently used for isolation of MDR S. aureus targeting mecA gene. Antibiotic susceptibility of S. aureus showed >90% isolates were sensitive to ciprofloxacin and trimethoprim and resistant against oxacillin, ampicillin, and cefoxitin. Further, 50-85% of the S. aureus were sensitive to gentamicin, oxytetracycline, and chloramphenicol and resistant against cefotaxime, vancomycin, and cefixime. Minimum inhibitory concentration (MIC) of cefotaxime, (C) and ampicillin (A) in combination with gentamicin (G) was reduced by 99.34% and 70.46%, respectively, while with chloramphenicol (Ch), reduction was 57.49% and 60%, respectively. In addition, the Fractional Inhibitory Concentration Index (FICI) of G+A, Ch+C and Ch+G combinations showed synergy against 80%, 60%, and 30% of MDR S. aureus, respectively. Similarly, C+A and Ch+G displayed indifferent interaction against 70 % and 30% of isolates, respectively, while the later showed additive interaction against 10% of MDR S. aureus. Altogether, our results described effective combination of gentamicin and chloramphenicol with ampicillin and cefotaxime to combat MDR S. aureus