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Abstract Cancer and related disorders are the most common cause of cancer-related mortality with the incidence of 1 in 9 among the pre-menopausal Pakistani females. among the most common ailments worldwide, indicating the importance of developing particular techniques that could help attenuate the effects of breast cancer and related outcomes. The primary aim of the current study was to review the role of inflammatory and stress markers in the development and progression of breast cancer. Four hundred ninety-eight (n = 498) patients with breast cancer and four hundred and ninety-eight (n = 498) age- and sex-matched controls were selected for this case‒control study. Serum samples were obtained, and the levels of stress and inflammatory markers, including Matrix metalloproteases (MMPs), Interleukins (ILs), Heat shock proteins (HSPs), Malondialdehyde (MDA), Nitric Oxide (NO), inducible Nitric Oxide Synthase (iNOS) and Tumour necrosis factor-alpha (TNF-α), were determined. Most (62%) patients had metastatic breast cancer (stage III or IV) with an adverse grade (65% with Grade III and 35% with Grade II). The present study showed that the levels of oxidants such as MDA, ILs, MMPs and HSPs were significantly greater, while the levels of antioxidants such as Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), vitamin A, C and D were significantly lower in breast cancer patients than in controls, suggesting their diagnostic importance and role in the pathophysiology of breast cancer. Oxidants, including IL-1, HSP27 and MMP9, which are highly specific and sensitive, may be used to develop the pathophysiological pathways of metastatic breast cancer in these patients. These pathways include cell invasion, cell migration and epithelial–mesenchymal transition. Therefore, we concluded that an increase in growth factors, e.g., Vascular Endothelial Growth Factor (VEGF), Tumour Growth Factor-beta (TGF-β) and B-cell lymphoma (Bcl2), under the influence of these variables plays a crucial role in the metastasis of breast cancer.

ABSTRACT Background: Oxidative stress and antioxidative status caused by hepatitis C therapy plays a significant role in aggravating the disease. A number of reactive oxygen species are responsible for the damaging of cell machinery and ultimately disturbing the homeostasis of the cell. Objectives: To assess enzymatic, non-enzymatic antioxidants and circulating biomarkers in HCV patients receiving interferon therapy. Methods: Study subjects were divided into two groups; patients and controls. The levels of the Thiobarbituric acid reactive substances (TBARS, as a marker of lipid peroxidation), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and lipid peroxidation product (MDA) in the serum were estimated. Results: There was statistically difference between patients and healthy controls in levels of CAT(p< 0.000**), SOD( p< 0.000**), GSH (p< 0.000**)and MDA(p< 0.000**). Similarly, the levels of ALT (p< 0.048*), AST (p< 0.005*) and ALP (p< 0.000**) were also statistically different between two groups. 1 Arif Malik Institute of Molecular Biology and Biotechnology, University of Lahore. 2 Muhammad Saeed Qureshi Department of Biochemistry, Allama Iqbal Medical College, Lahore. 3 Abdul Manan Institute of Molecular Biology and Biotechnology, University of Lahore. 4 Saadia Saleem Institute of Molecular Biology and Biotechnology, University of Lahore. 5 Mamoona Munir Institute of Molecular Biology and Biotechnology, University of Lahore. 6 Atiya Fatima Institute of Molecular Biology and Biotechnology, University of Lahore. 7 Mahwish Arooj Center for Research in Molecular Medicine, University of Lahore. 8 Muhammad Husain Qazi Center for Research in Molecular Medicine, University of Lahore. Corresponding Author Arif Malik Conclusion: Imbalanced levels of superoxide dismutase, catalase, reduced glutathione, MDA and serum enzymes (e.g. ALT, AST, ALP) revealed that interferon itself play a crucial rule in disturbing oxidative vs. antioxidative status which ultimately results in tissue damaging. Increased levels of MDA have a significant correlation with disease development during the course of therapy. KEY WORDS: ALT, AST ALP, Antioxidants, MDA (Malonyldialdehyde) Superoxide dismutase, Catalase, Reduced Glutathione.

Abstract The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds—sitosterol, amyrin, and epiafzelechin—alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand–protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160–200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with β-sitosterol (100 mg/kg b wt), β-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson’s correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds β-sitosterol, β-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon.

Abstract Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The emergence of drug resistance and other adverse effects in available anticancer options are challenging to explore natural sources. The current study was designed to decipher the Arnebia nobilis (A. nobilis) extracts for detecting phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, and in-silico prediction of potent anticancer compounds. The phytochemical analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) extracts of A. nobilis. ANH extract exhibited a better antioxidant potential to scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, which showed better potential only against H2O2 radicals. In 24 h treatment, ANH extract revealed higher cytotoxicity (IC50 value: 22.77 µg/mL) than ANH extract (IC50 value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the normal (BHK) cells using MTT assay. A better apoptotic potential was observed in ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, from which only 14 bioactive compounds were selected for molecular docking based on druggability criteria and toxicity filters. Among the five top scorers, deoxyshikonin exhibited the best binding affinities of − 7.2, − 9.2, − 7.2 and − 9.2 kcal/mol against TNF-α, TGF-βR1, Bcl-2 and iNOS, respectively, followed by ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their desirable ADMET properties. The phytochemicals of ANH extract could be used as a promising drug candidate for liver cancer after further validations.

Societal Impact Statement Sandalwood and other high value tree species are under significant threat from illegal harvest. Illegal logging is an increasing problem contributing to deforestation, biodiversity loss, human rights abuses and funding transnational crime. Successful prosecution of illegal logging is hindered by a lack of methods to provide evidence of the origin of timber. New analytical techniques have been developed to trace timber back to its source. These methods, together with the establishment of sustainable sources of forest resources, can help protect vulnerable species by providing evidence to prosecute illegal harvest and ensure that commercially available forest products come from sustainable sources. Summary Sandalwood is highly valued for its fragrant oil and has a long history of cultural and economic importance in many regions of the world. Historical overharvest and poor management have depleted natural populations of sandalwood, which are slow to regenerate. The increasing establishment of plantation sandalwood creates an alternative resource for the sandalwood industry while potentially relieving harvesting pressure on natural stands. Due to the high demand for sandalwood, remaining wild populations are still under threat from illegal logging and methods to identify the source of harvested sandalwood are needed. Laws and regulations aimed at preventing illegal harvest and possession of sandalwood have been put in place but cannot be enforced without the forensic tools to independently verify claimed origin or product quality. The high value of sandalwood combined with the difficulties in enforcing illegal logging laws makes these species particularly vulnerable to poaching. There is an immediate need to develop tools that can identify illegally sourced and adulterated sandalwood products. This paper reviews the current and developing scientific tools that can help identify and control illegal activity in sandalwood supply chains and provides recommendations for future research. Topics include isotope and DNA analysis for tracing illegally harvested sandalwood, chemical profiling for quality control of sandalwood oils, network and policy development to establish a framework for future regulation of the sandalwood trade.

Objectives: To explore if a positive association existed between breast cancer and increased breast density. Method: The retrospective cross-sectional study was conducted at Shifa International Hospital, Islamabad and comprised data from July 10, 2018, to July 10, 2020, of all patients who underwent mammography for screening or diagnostic purposes. Data was collected by reviewing patients’ charts, and was divided into diagnostic group A and screening group B according to mammography target. Breast Imaging Reporting and Data System category was also noted. Data was analysed using SPSS 21. Results: Of the 1,035 women with mean age 46.8±2.5 years (range: 35-82 years), 928(89.7%) were in group A and 107((10.3%) were in group B Prevalent breast densities overall were category A 67(6.3%), B 349(33.7%), C 530(51.2%) and D 89(8.5%). In group A, a lump was detected in 542(58.4%) patients. Of them, 367(67.7%) lesions were malignant and 175(32.3%) were benign. Breast density and malignant tumours had significant association (p

Abstract Widespread use of green synthesized silver nanoparticles (AgNPs) in pharmaceutical and cosmetics demand for its toxicological assessment. The current study describes the influence of exposure to kumquat, Fortunella margarita (FM) synthesized AgNPs in albino rats. Animals (n=60) were randomly distributed into four groups. Group, I served as control while groups II-IV were exposed to FM-AgNPs by the single intraperitoneal dose of 1, 5, and 10 mg/kg body weight, respectively. Animals were sacrificed at two-week intervals up to 5 weeks. Hematology, tissue (liver and spleen) oxidative stress biomarkers (SOD, CAT, and MDA), and histopathological examination were performed. Significant elevation in hemoglobin (Hb), Erythrocyte count (RBC), hematocrits (HCT), and hematological indices and depletion in total leukocytes count (TLC) was recorded at different time points. Similarly, a significant increase in SOD, CAT, and MDA activity was observed in both liver and spleen. But changes (p ≤ 0.005) in the spleen was recorded more consistently. Exposures to the high dose of FM-AgNPs lead to significant alterations in microanatomy of the liver and spleen. In liver vacuolization, enucleation, necrosis, congestion, and reduction in the size of cell, nucleus, portal vein, and elevation in cell density per unit area were recorded. In the spleen, except for enlargement in splenic sinuses, no other alterations could be recorded. It is concluded that FM-AgNPs leaves time and dose-dependent toxicity in rats but variations are more evident at high doses.

Introduction: Cadmium(Cd) an industrial poison present abundantly in the environment, causes human toxicity by an inflammatory process. Chronic exposure of cadmium can cause a number of molecular lesions that could be relevant to oncogenesis, through indirect or epigenetic mechanisms, potentially including abnormal activation of oncogenes and suppression of apoptosis by depletion of antioxidants. As induction of cyclooxygenase (COX)-2 is linked to inflammatory processes, use of luteolin, epiafzelechin, and albigenin alone or in different combinations may be used as anti-inflammatory therapeutic agents.Methods: We, herein, performed in silico experiments to check the binding affinity of phytochemicals and their therapeutic effect against COX-2 in cadmium administered rats. Wistar albino rats were given phytochemicals in different combinations to check their anti-inflammatory activities against cadmium intoxication. The level of alanine aminotransferases (ALT), 4-hydroxynonenal (4HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), isoprostanes (IsoP-2α), COX-2, and malondialdehyde (MDA) were estimated with their respective ELISA and spectrophotometric methods.Results: The generated results show that phytocompounds possessed good binding energy potential against COX-2, and common interactive behavior was observed in all docking studies. Moreover, the level of ALT, 4HNE, 8-OHdG, TNF-α, IsoP-2α, malondialdehyde, and COX-2 were significantly increased in rats with induced toxicity compared to the control group, whereas in combinational therapy of phytocompounds, the levels were significantly decreased in the group. Discussion: Taken together, luteolin, epiafzelechin, and albigenin can be used as anti-inflammatory therapeutic agents for future novel drug design, and thus it may have therapeutic importance against cadmium toxicity.

Background: Hypnosis is being used in combination with different forms of psychotherapy nowadays, such as neuro-linguistic programming, to work as a complementary treatment. This pairing allows for more targeted and patient-specific approaches to treat psychological disorders, phobias, and pain. An example is our previous study, in which hypnosis was used to treat tobacco-pan addiction. Following a similar model in this case study, we investigate the effectiveness of hypnosis and neuro-linguistic programming as treatments for anxiety and phobias. Case Presentation: We discuss a case of a 20-year-old boy with severe anxiety and social phobia who was already taking antipsychotic drugs and antidepressants, but they did not aid in treating his condition. He was then treated with hypnotherapy and neuro-linguistic programming to address the rooted triggers for his phobia. A thorough three-hour session revealed the details of each traumatic event. Each incident was isolated and changed in the patient's subconscious mind while he was hypnotized to remove that incident's role as a trigger. Management & Results: The patient reported approximately seventy percent recovery immediately after the first session in terms of rebuilding his confidence. The recovery was measured on DASS-21 and Rosenberg Self-Esteem Scale (RSES). The severity of his phobia was significantly controlled in a short-span of time, with almost no episode after the first hypnosis and NLP session. Conclusion: Hypnotherapy and neurolinguistic programming is an effective treatment for anxiety disorder and social phobia. It is also time-efficient and produces better results than other forms of treatment without accompanying side effects.

الملخص: أهداف البحث: تتزايد التهابات المسالك البولية في الأطفال بسرعة في جميع أنحاء العالم، وعادة ما تكون ناجمة عن البكتيريا المقاومة للأدوية. هذه الدراسة تحدد انتشار التهاب المسالك البولية في الأطفال، وتقيم نمط البكتيريا المقاومة للأدوية من قبل سلالات معزولة من الإشريكية والكلبسيلة عن التهابات المسالك البولية في مرضى الأطفال. طرق البحث: تم عزل السلالات البكتيرية الممرضة للجهاز البولي من المرضى الأطفال بالتهابات المسالك البولية التي تم إدخالها في معهد صحة الطفل بلاهور، باكستان. تم تحديد السلالات من جنس الإشريكية والكلبسيلة، من خلال التوصيف الكيميائي الحيوي، وتعرضت لمقاييس الحساسية للمضادات الحيوية لتحديد البكتيريا المقاومة للأدوية ضد ٢١ من الأدوية المضادة للميكروبات. النتائج: خلال ستة أشهر، تم عزل ما مجموعه ٦٣ من الإشريكية و٣٧ من سلالات الكلبسيلة من ١٣٠ طفلا مصابين بالتهابات المسالك البولية. وأظهرت مقاييس حساسية المضادات الحيوية أن الإشريكية والكلبسيلة لها مقاومة عالية ضد كوأموكسيكلاف، وسيفروكسيم، وسيفيكسيم، وسيفوتاكسيم، وسيفتازيديم، وسيفترياكسون، وسيبروفلوكساسين، وحمض ناليديكسيك، ونورفلوكساسين، وحمض بيبيديمك، وكوتريموكسيزول. ومع ذلك، فقد وجد أن للعقاقير المضادة للميكروبات بما في ذلك بوليميكسين-ب، وكبريتات الكوليستين، والكلورامفينيكول، ونيتروفوارانتون، وفوسفومايسين فاعلية كبرى للتحكم بالسلالات الممرضة للجهاز البولي من القولونية الإشريكيشية والكلبسيلة الرئوية. وتم تحديد السلالات الخمس التي تعاني من أعلى مقاومة ضد المضادات الحيوية المختبرة على أنها سلالات من الإشريكية القولونية والكلبسيلة الرئوية. الاستنتاجات: أظهرت دراستنا أن الإشريكية القولونية والكلبسيلة الرئوية كانت البكتيريا المهيمنة لمقاومة للأدوية من التهابات المسالك البولية المكتسبة من المجتمع في مجموعتنا. وتم الوصول إلى أن هذه البكتيريا الممرضة للجهاز البولي غير مستجيبة للعقارات المستخدمة بشكل روتيني من المضادات الحيوية مثل بيتا اللاكتام، والبيريدوبيريميدين، والكينولون، والفلوروكينولون. قد تكون هذه النتائج مفيدة للأطباء لتعزيز العلاج التجريبي لالتهابات المسالك البولية في الأطفال. Abstract: Objectives: Urinary tract infections (UTIs) in children are rapidly increasing worldwide and are commonly caused by extensively drug-resistant bacteria. This study determines the prevalence of UTIs in paediatric patients and evaluates the pattern of extensively drug-resistance in Escherichia coli and Klebsiella pneumoniae strains isolated from paediatric UTI patients. Methods: Uropathogenic bacterial strains were isolated from paediatric patients with UTIs admitted to the Institute of Child Health, Lahore, Pakistan. Strains of both E. coli and K. pneumoniae were identified using biochemical characterisation and subjected to antibiotic susceptibility assays for 21 common antimicrobial drugs in order to determine their extensively drug-resistant profile. Results: We isolated 63 E. coli and 37 K. pneumoniae strains from 130 paediatric patients with UTIs over a period of six months. The antibiotic susceptibility assays showed that both the E. coli and K. pneumoniae strains exhibited a high degree of resistance against co-amoxiclav, cefuroxime, cefixime, cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, nalidixic acid, norfloxacin, pepedemic acid, and co-trimoxazole. However, several of the antimicrobial agents, including polymyxin B, colistin sulphate, chloramphenicol, nitrofurantoin, and fosfomycin, were found to retain their antimicrobial activities against both pathogens. The five highest antibiotic resistant strains were identified as E. coli strains ZK9, ZK40, and ZK60 and K. pneumoniae ZK32 and ZK89 using 16S rRNA gene sequencing. Conclusion: Our study demonstrates that E. coli and K. pneumonia are the dominant extensively drug-resistant uropathogenic bacteria in community-acquired UTIs in our cohort. These uropathogens were found to be resistant to the majority of the routinely-used classes of β-lactams, pyridopyrimidines, quinolones, and fluoroquinolone antibiotics, and these findings may be useful for clinicians in their treatment of paediatric UTIs.

Optimal sizing is necessary in hybrid renewable energy systems for the system to work with highest reliability and minimum cost. The street light system inside Sultan Qaboos University in Oman is considered as a case study for optimal sizing of PV/battery system for three different types of lamps, HPS, LED and discrete LED. The life cycle cost analysis and cost per kWh for two different configurations of panel and battery, the first with larger sized panel/battery and the second, smaller sized panel/battery with and without considering the number of autonomous days(NAD) is compared to investigate the economic feasibility of implementing the system in Oman. Genetic algorithm tool in MATLAB is used for optimal sizing, adopting loss of power supply(LPS) to gauge the reliability using actual data existing in Oman. The cost per kWh of generated energy with large panel/battery system was found to be 0.08 $/kWh while it was 19.9 $/kWh considering the same case for small panel/battery system proving the economic feasibility of implementing the large panel/battery system in Oman. Results also prove that higher the energy requirement, higher the LCC but lesser the cost per kWh. The conversion of the grid connected street light system extending a stretch of 8.6 km with 285 HPS lamps of 400 W to PV/battery system with LED lamp of 80W is expected to reduce the CO2 emissions by 133.595 tonnes annually. The results can be applied to practical systems worldwide to save millions of dollars and CO2 emissions.

الملخص: أهداف البحث: تهدف هذه الدراسة لتحديد مدى انتشار التهابات المسالك البولية عند الحوامل وتوصيف السلالات البكتيرية المسببة للأمراض البولية المرتبطة مع البيلة الجرثومية المصحوبة وغير المصحوبة بأعراض في لاهور، الباكستان. طرق البحث: بين ديسمبر ٢٠١٨ ويونيو ٢٠١٩، قمنا بتحليل السلالات البكتيرية المسببة للأمراض البولية من عينات البول الوسطية لعدد ٨٠ سيدة حامل. وكانت الفئة العمرية للسيدات الحوامل من ١٩-٤٥ عاما وينتمون إلى المناطق الحضرية والريفية. كما قمنا أيضا بتسجيل العوامل الاجتماعية والاقتصادية لهذه المجموعة. وتم التعرف على السلالات المعزولة ظاهريا وتقييمها لنمط مقاومة الأدوية المتعددة ضد الأدوية المضادة للميكروبات الموصى بها. النتائج: من بين ٨٠ سيدة حامل، كان ٦٥ لديهن التهابات المسالك البولية، ما يعكس انتشار (٨١٪) التهابات المسالك البولية عند السيدات أثناء الحمل. وكانت أعمار أغلب المشاركات ٢٤-٣٥ عاما، ومتعددات الحمل، وكن في الثلث الثالث من الحمل. كما أظهرت النتائج أن ٦٧ من السلالات البكتيرية المسببة للأمراض البولية تنتمي إلى الإشريكية القولونية (٣١٪)، والكلبسيلة الرئوية (٢٣٪)، والبكتيريا الزائفة (١٦٪)، والبكتيريا العقدية (٤٪) والمكورات المعوية (٤٪)، والمكورات العنقودية (٤٪)، والبكتيريا المتقلبة (٣٪). كما تم تحديدهم من خلال التوصيف الكيميائي الحيوي. ولوحظ أن أعلى أنماط المقاومة الإجمالية للأموكسيسيلين، وحمض البيبميديك، والأمبيسلين ضد الإشريكية القولونية، وحمض البيبميديك، والأمبيسلين، وسيفوتاكسيم ضد الكلبسيلة الرئوية، وسيبروفلوكساسين وسيفوتاكسيم ضد الزائفة. وتم تحديد ثلاثة أعلى سلالات لمقاومة الأدوية المتعددة التي كانت من سلالة الزائفة الزنجارية، وسلالة الإشريكية القولونية، وسلالة الكلبسيلة الرئوية. الاستنتاجات: في هذه الدراسة، أظهرت السلالات المسببة لأمراض الجهاز البولي أعلى نمط لمقاومة الأدوية المتعددة. العلامات المقلقة لأمراض الجهاز البولي المقاومة للأدوية المتعددة نادرا ما يتم تناولها والاهتمام العاجل بهذه المسألة أمر ضروري. Abstract: Objectives: This study aimed to determine the prevalence of urinary tract infections (UTI) in pregnant women and characterise the uropathogenic bacterial strains associated with symptomatic and asymptomatic bacteriuria in Lahore, Pakistan. Methods: Between December 2018 and June 2019, we analysed the uropathogenic bacterial strains from midstream urine samples in 80 pregnant women. The age of the pregnant women ranged from 19 to 45 years, and they resided in urban and rural areas. We also recorded socioeconomic factors in this cohort. The isolated strains were phenotypically identified and evaluated for multiple drug resistance (MDR) patterns against recommended antimicrobial drugs. Results: Of the 80 pregnant women, 65 had UTI, reflecting an 81% prevalence of UTI in women during pregnancy. The majority of participants aged 24–35 years, were multipara, and were in their third trimester. Results showed that 67 uropathogenic bacterial strains belonged to Escherichia (31%), Klebsiella (23%), Pseudomonas (16%), Streptococcus (4%), Enterococcus (4%), Staphylococcus (4%), and Proteus (3%) genera, as identified using biochemical characterisation. The highest overall resistance of Escherichia was seen against amoxicillin, pipemidic acid, and ampicillin; for Klebsiella against pipemidic acid, ampicillin, and cefotaxime; and for Pseudomonas against ciprofloxacin and cefotaxime. The three strains with the highest MDR were identified using 16S rRNA as Pseudomonas aeruginosa strain UA17, Escherichia coli strain UA32, and Klebsiella pneumoniae strain UA47. Conclusion: In this study, the MDR uropathogenic strains showed the highest resistance pattern. The alarming signs of MDR uropathogenic infections are infrequently addressed and thus, urgent attention to this matter is essential.

Abstract Background Moringa oleifera is a common vegetable in many countries since ancient times, possesses numerous phenolic compounds having a wide array of biological activities. It possesses anticancer activity that can be used to develop new drugs for treatment of various types of cancers. The current study was conducted to evaluate the composition of phenolic compounds and in vitro and in silico anticancer activities of M. oleifera leaves extracts. The leaves of M. oleifera were subjected to extraction for solvent fraction using n-hexane, chloroform, ethyl acetate, butanol, and aqueous solvents. The solvent fractions were tested for anticancer activity in vitro against Hela cancer cell line and screened for phenolic compounds through reversed-phase high-performance liquid chromatography. The molecular docking approach was employed to check binding conformations of phytochemicals against the target protein. Result The result revealed that all the solvent fractions possess in vitro anticancer activity against Hela cancer cell line. The n-hexane fraction showed a 50% reduction in Hela cancer cell viability at 416 μg mL−1 as compared to control. The extracts of solvent-fraction contained 10 phenolic compounds viz. quercetin, gallic acid, sinapic acid, vanillic acid, 4-hydroxy-3-methoxy benzoic acid, p-coumaric acid, m-coumaric acid, 4-hydroxy-3-methoxy cinnamic acid, caffeic acid, and syringic acid. Molecular docking studies revealed that the ligands bind within the active site of target protein have good binding energy values. Conclusion This study shows that M. oleifera leaves may have the potential to inhibit cancer cell growth and improving human health in addition to food ingredient innovations. Based on in vitro and in silico results, the phytochemicals from M. oleifera leaves can be used as leading drugs to treat cancer. Graphical abstract

Salinity is an important adverse environmental problem that caused a loss in the sense of reducing yield per plant, morphological, and physiological functions of crop plants. The plants compete with environmental stress conditions to withstand following normal growth and development. The exchange of cations or protons (H+) takes place across the cell membrane to maintain the osmotic pressure of cells under salt stress conditions. There is a huge number of cation/H+ antiporter 1 protein-producing gene by plant cells under salt stress conditions has been identified. However, a few have been characterized and sequenced which contributes to ion homeostasis and osmotic adjustment of cells. These cation/H+ antiporters are produced and stored in the vacuoles, endosomal forms and in the cytoplasm. The cation/H+ antiporters are involved in the homeostasis of K+, Na+, and pH of the cell under salinity stress conditions. The cation/H+ antiporters help plants cells to regulate all physiological functions under salt stress conditions.

The world is struggling to deal with the corona pandemic. Effective therapies are still awaited due to the lack of understanding of the pathophysiological mechanism of the disease. Bearing recent research and clinical observations in mind, the authors propose a novel physiological mechanism of COVID-19 and explain development of COVID-19 related acute respiratory distress syndrome (ARDS) secondary to COVID-19 related hemoglobinopathy. It is a consistent observation that the radiological picture of COVID-19 related ARDS bears more resemblance to high altitude pulmonary edema (HAPE) than typical ARDS. There has been great controversy regarding this proposed similarity. The main argument from those objecting to this comparison is that the etiology is hypoxia in case of HAPE and inflammation in COVID-19 related ARDS. We propose that considering the recent bioinformatics prediction models, COVID-19 might first infect red blood cells via CD147 and cause hemoglobin damage. The resulting hypoxemia may cause pulmonary hypoxic vasoconstriction leading to HAPE-like lung lesions. The now introduced alveolar hypoxia further exaggerates hemoglobinopathy hypoxemia leading to a vicious cycle. In this review, the authors recommend laboratory experiments to prove these hypotheses. The proposed physiological mechanism has significant therapeutic implications. If proven, the authors suggest the use of exchange transfusion as adjunct therapy and development of anti-CD147 drugs.

In this work, laser shock peening (or simply laser peening) is investigated for the first time as a post welding treatment for dissimilar foils joined via the fully-mechanical, high-velocity laser impact welding technique. Single and double laser peening shots were applied to laser-impact-welded foils using three different metallic material combinations. Subsequent lap shear testing showed that single-shot laser peening increased the average weld strength by 12% to 25%, depending on the flyer and target material combination. In contrast, with double-shot laser peening, the average weld strength decreased regardless of the flyer and target materials involved. Scanning electron microscope images revealed wavy weld interfaces and increased interlocking between the foils for the single-shot laser peening treatments as compared to the initial “flat” weld interface geometry, thereby leading to greater flyer/target weld strength. In the double-shot laser peening treatments, however, separations and melting were observed along the weld interface due to rebounding and excessive plastic heat dissipation of the foils. The findings of this study reveal the first insights and effects regarding the application of laser shock peening as a post-welding treatment beyond conventional fusion-based welding to high-velocity impact welding methods.

Background: A recent COVID-19 pandemic has resulted in a large death toll rate globally and even no cure or vaccine has been successfully employed to combat this disease. Patients have been reported with multi-organ dysfunction along with acute respiratory distress syndrome which implies a critical situation for patients and made them difficult to breathe and survive. Moreover, pathology of COVID-19 is also related to cytokine storm which indicates the elevated levels of interleukin (IL)-1, IL-6, IL-12, and IL-18 along with tumor necrosis factor (TNF)-α. Among them, the proinflammatory cytokine IL-6 has been reported to be induced via binding of severe acute respiratory syndrome coronavirus 2 (SARS)-CoV-2 to the host receptors. Methodology: Interleukin-6 blockade has been proposed to constitute novel therapeutics against COVID-19. Thus, in this study, 15 phytocompounds with known antiviral activity have been subjected to test for their inhibitory effect on IL-6. Based on the affinity prediction, top 3 compounds (isoorientin, lupeol, and andrographolide) with best scores were selected for 50 ns molecular dynamics simulation and MMGB/PBSA binding free energy analysis. Results: Three phytocompounds including isoorientin, lupeol, and andrographolide have shown strong interactions with the targeted protein IL-6 with least binding energies (−7.1 to −7.7 kcal/mol). Drug-likeness and ADMET profiles of prioritized phytocompounds are also very prominsing and can be further tested to be potential IL-6 blockers and thus benficial for COVID-19 treatment. The moelcular dynamics simulation couple with MMGB/PBSA binding free energy estimation validated conformational stability of the ligands and stronger intermolecular binding. The mean RMSD of the complexes is as: IL6-isoorientin complex (3.97 Å ± 0.77), IL6-lupeol (3.97 Å ± 0.76), and IL6-andrographolide complex (3.96 Å ± 0.77). In addition, the stability observation was affirmed by compounds mean RMSD: isoorientin (0.72 Å ± 0.32), lupeol (mean 0.38 Å ± 0.08), and andrographolide (1.09 Å ± 0.49). A similar strong agreement on systems stability was unraveled by MMGB/PBSA that found net binding net ~ −20 kcal/mol for the complexes dominated by van der Waal interaction energy. Conclusion: It has been predicted that proposing potential IL-6 inhibitors with less side effects can help critical COVID-19 patients because it may control the cytokine storm, a major responsible factor of its pathogenesis. In this study, 3 potential phytocompounds have been proposed to have inhibitory effect on IL-6 that can be tested as potential therapeutic options against SARS-CoV-2.

Duqm is located in the Al Wasta Governorate in Oman and is currently fed by 10 diesel generators with a total capacity of around 76 MW and other rental power sources with a size of 18 MW. To make the electric power supply come completely from renewables, one novel solution is to replace the diesel with hydrogen. The extra energy coming from the PV-wind system can be utilized to produce green hydrogen that will be utilized by the fuel cell. Measured data of solar insolation, hourly wind speeds, and hourly load consumption are used in the proposed system. Finding an ideal configuration that can match the load demand and be suitable from an economic and environmental point of view was the main objective of this research. The Hybrid Optimization Model for Multiple Energy Resources (HOMER Pro) microgrid software was used to evaluate the technical and financial performance. The findings demonstrated that the suggested hybrid system (PV-wind-fuel cell) will remove CO2 emissions at a cost of energy (COE) of USD 0.436/kWh and will reduce noise. With a total CO2 emission of 205,676,830 kg/year, the levelized cost of energy for the current system is USD 0.196/kWh. The levelized cost for the diesel system will rise to USD 0.243/kWh when taking 100 US dollars per ton of CO2 into account. Due to system advantages, the results showed that using solar, wind, and fuel cells is the most practical and cost-effective technique. The results of this research illustrated the feasibility and effectiveness of utilizing wind and solar resources for both hydrogen and energy production and also suggested that hydrogen is a more cost-effective long-term energy storage option than batteries.

Background: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidative stress and increase in reactive oxygen species result in 8-oxodG production which induces apoptosis of both astrocytes and thyrocytes thus predisposing them to thyroid dysfunction and neurodegeneration. Furthermore, the presence of excessive free radicals increases thyroid thermogenesis causing hyperthyroidism or its excess may cause hypothyroidism by inhibiting iodide uptake. In the present study, we evaluated the various biomarkers associated with thyroid dysfunction in schizophrenics.Materials and Methods: 288 patients suffering from schizophrenia and 100 control subjects were screened for liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). Also, the stress markers, namely malondialdehyde (MDA), homocysteine, cysteine, methionine, the thyroid profile including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyroxine peroxide antibody (TPO-Ab); TSH receptor-Ab (TSHr-Ab), dietary antioxidants, lipids, cytokines, aminoacids and hormones, vitamins and trace elements, and other biochemical parameters.Results: The LFTs showed elevated levels of ALT (45.57 ± 4.87 Vs. 26.41 ± 3.76 U/L), AST (40.55 ± 1.34 Vs. 21.92 ± 3.65 U/L), ALP (121.54 ± 4.87 Vs. 83.76 ± 5.87 U/L), and total bilirubin (2.63 ± 0.987 Vs. 1.10 ± 0.056 mg/dl), in schizophrenics than controls. Increased levels of MDA (3.71 ± 0.967 Vs. 1.68 ± 0.099) and homocysteine (17.56 ± 2.612 Vs. 6.96 ± 1.987 μmol/L were observed in schizophrenics compared to the controls, indicating increased stress. Levels of cysteine and methionine were decreased in schizophrenics than the controls (1.08 ± 0.089 Vs. 4.87 ± .924 μmol/L and 17.87 ± 1.23 Vs. 99.20 ± 5.36 μmol/L). The levels of TPO-Ab (IU/ml), Tg-Ab (pmol/L), and TSHr-Ab (IU/L) were observed to be higher in the patients’ group as compared to control subjects (9.84 ± 2.56 Vs. 5.81 ± 1.98, 55.50 ± 2.98 Vs. 32.95 ± 2.87 and 2.95 ± 0.0045 Vs. 1.44 ± 0.0023 respectively). Levels of Vitamin B6, B9, and B12 were also significantly decreased in the patients compared to the healthy controls.Conclusion: The schizophrenics, demonstrated altered liver function, increased stress markers, and decreased dietary antioxidants. Reduced primary and secondary antioxidant levels, may result in hyperhomocysteinemia and cause further DNA and mitochondrial damage. Therefore, homocysteine and/or prolactin levels may serve as candidate prognostic markers for schizophrenia. Also, both neurological symptoms and the susceptibility to thyroid disorders may be prevented in the initial stages of this debilitating disorder by appropriate dietary supplementation of antioxidants which can rectify a reduction in primary and secondary antioxidants, and disturbed prolactin-serotonin-dopamine interactions in schizophrenics.

Introduced is a comprehensive numerical modeling framework that includes microstructure when simulating the laser impact welding (LIW) of metals to study the transient phenomena that occur during weld formation. Such transient phenomena include evolution of shear stresses, plastic strains, thermal response, and material jetting. Inhomogeneous microstructures for two dissimilar foils (aluminum 1100 and stainless steel 304) are first predicted using the Dynamic Kinetic Monte Carlo (KMC) method to simulate laser-based powder bed fusion (PBF-LB) additive manufacturing (AM). These microstructures are subsequently incorporated into an Eulerian finite element (FE) simulation of the LIW process, enabling prediction of grain elongations that result from the varying yield surfaces, stacking fault energies, and grain-boundary sliding effects. Trends in the predicted microstructure deformation patterns show strong agreement with those from experimental images in the literature. Compared to existing homogeneous models, the new framework with inhomogeneous AM microstructure reveals higher collision velocities at the weld interface, resulting in increased plastic strain rates, greater plastic heat dissipation, and increased material jetting with higher jet temperatures. The framework allows for new opportunities to study correlations between grain topography (as well as polycrystalline metal texture) and the transient process phenomena occurring at the impact weld interface.

Background: Pancreatic β-cells for insulin secretion are the main regulators of mammalian metabolic process. Diabetes and hyperglycemia make the patient dependable on exogenous insulin, which is due to the lack of functional β-cells. Oxidative stress also play an important role in the aggravation of this pathological condition. Recent insights into the development of β-cells along with the pluripotent stem cells discovery have opened new ways to generate β-cells that can help in the screening of various drugs and also in the transplantation therapy since, these pluripotent Embryonic Stem Cells (ESCs) can develop in any type of cell, due to which any defective tissue can be substituted. Objectives: The objective of this study was to evaluate current strategies which can help to control diabetes mellitus. Methodology: Methodological approach of this review was based on the comparison of theoretical studies and researches related to diabetes mellitus. Results: In vitro or in vivo replication might be repeated based on proteins or through small molecules. Efforts have been made through which differentiated cells can be converted into β-cells by transcriptional regulators that are the significant players for the development, as well as responsible to identify conditions that cause replication of β-cell both in vitro and in vivo. The recent strategies can be applied for new β-cells generation and also highlights the future aspects regarding the mechanisms that govern later differentiation stages. Conclusion: This review provides an update on generating β-cells from different strategies and also brief about the development and function of β-cells that how they could help to control diabetes.

A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein. The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. The S1 and S2 domains of spike proteins were analyzed, and two vaccine constructs were prioritized with T-cell and B-cell epitopes. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4.

Antimicrobial resistance (AMR) compelled scientists in general while pharmacists, chemists and biologists in specific to believe that we could always remain ahead of the pathogens. The pipeline of new drugs is running gasping and the inducements to develop new antimicrobials to address the global problems of drug resistance are weak. In this pursuit, effective endeavours to prepare new anti-bacterial entities is highly wished. The present study demonstrates successful synthesis of a library of 1,4-disbustituted 1,2,3-triazoles (3a-3k) using Click-chemistry concept and anti-their bacterial potential. In this 1,3-dipolar cycloaddition, the 3-methoxy-4-(prop-2-yn-1-yloxy)benzaldehyde (1) was used as alkyne partner which was synthesized from vanillin and propargyl bromide and further reacted with differently substituted arylpropoxy azides (2a-k) to furnish series of mono and bis1,4-disubstituted-1,2,3-triazoles. All the synthesized compounds were characterized spectroscopically and were evaluated for their initial antimicrobial activity. Preliminary results of antibacterial screening revealed that the synthesized compounds have the highest inhibitory effects compare to the control ciprofloxacin. The compounds 3b and 3g were found to be the most active (MIC: 5 μg/mL, MIC: 10 μg/mL respectively) against various strains of gram-positive and gram-negative bacteria. The molecular docking study against 4GQQ protein with synthesized ligands was performed to see the necessary interactions responsible for anti-bacterial activity. The docking analysis of the most potent compound 3g supported the antibacterial activity exhibiting high inhibition constant and binding energy.

Objective: To evaluate correlation between the levels of vitamin D and male infertility as well as to determine the efficacy of vitamin D in improving the male fertility by up-regulating the levels of testosterone and spermatogenesis.Methods: In the present study, 130 male patients (aged 25-70 years) having fertility defects were screened and 145 healthy individuals were taken as control. All human subjects were screened for 4-hydroxynonenal, isoprostane-F2α, 8-hydroxy-2'-deoxyguanosine, vitamin D, luteinizing hormone, follicle stimulating hormone, testosterones, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and nitric oxide.Results: The screening analysis revealed that the levels of luteinizing hormone, follicle stimulating hormone, and testosterone were lower in male infertile subjects compared to healthy subjects. Similarly, the levels of vitamin D [(17.17 ± 2.30) ng/mL] and calcium[(6.29 ± 0.31) mg/dL] were significantly lower in infertile groups compared to the normal healthy groups. Moreover, the study revealed that the levels of superoxide dismutase, catalase, and glutathione peroxidase were significantly higher in healthy subjects compared to the infertile subjects.Conclusions: Vitamin D exhibits strong relevance to male fertility by maintaining the levels of sex hormones (luteinizing hormone, follicle stimulating hormone, and testosterone), up-regulating the antioxidant defense (superoxide dismutase, catalase, and glutathione peroxidase), and down-regulating the oxidative stress (malondialdehyde, nitric oxide, and inducible nitric oxide synthase species).

In this paper, two aspects related to streetlight systems are considered. In the first part, the economic analysis of replacing existing HPS lamps with light-emitting diode (LED) and discrete LED lamps for street lighting is performed using actual data from Oman. The street lighting system inside Sultan Qaboos University is considered for the case study. The discounted payback period, which is calculated to study the practicability of implementing the system, is found to be 1.01 years, making the system financially appealing. Moreover, the estimated reduction of a carbon footprint shows that tonnes of CO2 emissions are reduced, which makes it environmentally attractive. The second part of the paper considers optimal sizing of PV/battery system for a new streetlight system with LED lamps. The life cycle cost analysis was performed and the related cost of energy generated per kWh is estimated as 0.097 $/kWh which proves the economic viability of the system to be implemented in Oman besides minimizing the CO2 emissions to zero.

Medicinal plants of Moraceae family have been well-recognized traditionally due to their versatile applications in various fields including agriculture, cosmetic and food as well as in pharmaceutical industries. Their biomedical and medicinal importance is reflected from their broad range of pharmacological activities for treatment of various inflammatory conditions, cancer, infectious diseases, and gastrointestinal disorders. The present review was aimed to summarize and critically discuss the biomedical implications of Morus species, their bioactive compounds, and phytochemicals. Bioactivity guided fractionation of these medicinal plants revealed that different types of bioactive phytochemicals and secondary metabolites such as steroids, saponins, alkaloids, glycosides and phenolic compounds including terpenoids, flavonoids, anthocyanins and tannins were present. The critical analysis of the literature revealed that the aqueous, methanolic, and ethanolic extracts of Morus species and their bioactive compounds exhibit remarkable anti-oxidative, anti-diabetic, anti-stress, nephroprotective, antimicrobial, anti-mutagenic, anticancer, anxiolytic, hepatoprotective, anthelmintic, antimicrobial, immune-modulatory and cholesterol lowering effects. Based on the literature review and bioactivity guided investigation of Morus species and their phytomedicinal effects, we anticipate that these herbal products hold excellent potential for future research.

The use of chemicals around the globe in different industries has increased tremendously, affecting the health of people. The modern world intends to replace these noxious chemicals with environmental friendly products for the betterment of life on the planet. Establishing enzymatic processes in spite of chemical processes has been a prime objective of scientists. Various enzymes, specifically microbial proteases, are the most essentially used in different corporate sectors, such as textile, detergent, leather, feed, waste, and others. Proteases with respect to physiological and commercial roles hold a pivotal position. As they are performing synthetic and degradative functions, proteases are found ubiquitously, such as in plants, animals, and microbes. Among different producers of proteases, Bacillus sp. are mostly commercially exploited microbes for proteases. Proteases are successfully considered as an alternative to chemicals and an eco-friendly indicator for nature or the surroundings. The evolutionary relationship among acidic, neutral, and alkaline proteases has been analyzed based on their protein sequences, but there remains a lack of information that regulates the diversity in their specificity. Researchers are looking for microbial proteases as they can tolerate harsh conditions, ways to prevent autoproteolytic activity, stability in optimum pH, and substrate specificity. The current review focuses on the comparison among different proteases and the current problems faced during production and application at the industrial level. Deciphering these issues would enable us to promote microbial proteases economically and commercially around the world.

Cancer invasion involves a series of fundamental heterogeneous steps, with each step being distinct in its type regarding its dependence on various oncogenic pathways. Over the past few years, researchers have been focusing on targeted therapies to treat malignancies relying not only on a single oncogenic pathway, but on multiple pathways. Scientists have recently identified potential targets in the human genome considered earlier as non-functional but the discovery of their potential role in gene regulation has put new insights to cancer diagnosis, prognosis and therapeutics. Non coding RNAs (ncRNAs) have been identified as the key gene expression regulators. Long non-coding RNA (lncRNAs) reveal diverse gene expression profiles in benign and metastatic tumours. Improved clinical research may lead to better knowledge of their biogenesis and mechanism and eventually be used as diagnostic biomarkers and therapeutic agents. Small non coding RNAs or micro RNA (miRNA) are capable of reprogramming multiple oncogenic cascades and, thus, can be used as target agents. This review is aimed to give a perspective of non coding transcription in cancer metastasis with an eye on rising clinical relevance of non coding RNAs and their mechanism of action focusing on potential therapeutics for cancer pathogenesis. Keywords: Metastasis, Oncogene, microRNA, Oncomirs, Transcription, Genetic expression

Diabetes is one of the alarming health problem in Pakistan. According to international diabetes federation (IDF), about 7 million Pakistanis are victims of diabetes accounting a total of 3% population. Most of Pakistanis still prefer to use herbal medicines for almost all of their health issues. Aegle marmelos (commonly known as the bael tree) is highly reputed ayurvedic medicinal tree as it has been used in traditional medicine for centuries. In this pre-clinical work, 32 mice were induced for diabetes via injecting alloxan intraperitoneally at a dose of 100 mg/kg body weight and mice having 104-170 mg/dl sugar level were considered diabetic. All mice were divided into two groups, each group with three sub-groups containing normal, control and diabetic mice. One group was given normal feed whereas other group was given a food containing Aegle marmelos leaf extract at 300 mg/kg body weight as an effective dose against alloxan induced hyperglycemia. The experiments lasted for 60 days and blood samples (05 ml to 1.0 ml) were collected from coccygeal vein of rats on 1st day, 30th day and 60th day of the experiment in heparinized tubes and blood glucose level was measured using spectrophotometer by enzymatic kit at a wavelength of 540nm. It was observed that the Aegle marmelos leaf extract is an effective herbal remedy in reducing and maintaining the glucose level in normal and hyperglycemic mice

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia, excessive acetylcholinesterase (AChE) activity, formation of neurotoxic amyloid plaque, and tau protein aggregation. Based on literature survey, we have shortlisted three important target proteins (AChE, COX2, and MMP8) implicated in the pathogenesis of AD and 20 different phytocompounds for molecular docking experiments with these three target proteins. The 3D-structures of AChE, COX2, and MMP8 were predicted by homology modeling by MODELLER and the threading approach by using ITASSER. Structure evaluations were performed using ERRAT, Verify3D, and Rampage softwares. The results based on molecular docking studies confirmed that there were strong interactions of these phytocompounds with AChE, COX2, and MMP8. The top three compounds namely Albiziasaponin-A, Iso-Orientin, and Salvadorin showed least binding energy and highest binding affinity among all the scrutinized compounds. Post-docking analyses showed the following free energy change for Albiziasaponin-A, Salvadorin, and Iso-Orientin (−9.8 to −15.0 kcal/mol) as compared to FDA approved drugs (donepezil, galantamine, and rivastigmine) for AD (−6.6 to −8.2 Kcal/mol) and interact with similar amino acid residues (Pro-266, Asp-344, Trp-563, Pro-568, Tyr-103, Tyr-155, Trp-317, and Tyr-372) with the target proteins. Furthermore, we have investigated the antioxidant and anticholinesterase activity of these top three phytochemicals namely, Albiziasaponin-A, Iso-Orientin, and Salvadorin in colchicine induced rat model of AD. Sprague Dawley (SD) rat model of AD were developed using bilateral intracerebroventricular (ICV) injection of colchicine (15 μg/rat). After the induction of AD, the rats were subjected to treatment with phytochemicals individually or in combination for 3 weeks. The serum samples were further analyzed for biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), matrix metalloproteinase-8 (MMP-8), isoprostanes-2 alpha (isoP-2α), and acetylcholine esterase (AChE) using conventional Enzyme Linked Immunosorbent Assay (ELISA) method. Additionally, the status of lipid peroxidation was estimated calorimetrically by measuring thiobarbituric acid reactive substances (TBARS). Here, we observed a statistically significant reduction (P < 0.05) in the oxidative stress and inflammatory markers in the treatment groups receiving mono and combinational therapies using Albiziasaponin-A, Iso-Orientin, and Salvadorin as compared to colchicine alone group. Besides, the ADMET profiles of these phytocompounds were very promising and, hence, these potential neuroprotective agents may further be taken for preclinical studies either as mono or combinational therapy for AD.

BackgroundColorectal cancer (CRC) is the third most common type of cancer and leading cause of death worldwide. Major risk factors involved in the development of CRC are increased dietary sources, genetics, and increasing age. Purpose of the study was to find the role of different variables in the progression of CRC.Methodology50 blood samples from CRC patients and 20 samples from control were collected. Serum was separated from the blood by centrifugation. This serum was assessed for several antioxidants like superoxide dismutase (SOD), glutathione, glutathione peroxidase, glutathione reductase, catalase, vitamin A, C, and E, and pro-oxidants such as malondialdehyde, advanced oxidation protein products (AOPPs), and AGEs according to their respective protocols. Matrix metalloproteinase-7 (MMP-7) and isoprostanes were assessed by ELISA kits.ResultsLower levels of GSH (4.86 ± 0.78 vs 9.65 ± 1.13 μg/dl), SOD (0.08 ± 0.012 vs 0.46 ± 0.017 μg/dl), CAT (2.45 ± 0.03 vs 4.22 ± 0.19 μmol/mol of protein), and GRx (5.16 ± 0.06 vs 7.23 ± 0.36 μmol/ml) in the diseased group were recorded as compared with control. Higher levels of GPx (6.64 ± 0.19 mmol/dl) were observed in the subjects in comparison with control group (1.58 ± 0.30 mmol/dl). Highly significant decreased levels of vitamin A (0.81 ± 0.07 vs 2.37 ± 0.15 mg/ml), vitamin E (15.42 ± 1.26 vs 25.96 ± 2.19 mg/ml), and vitamin C (47.67 ± 7.69 vs 80.37 ± 10.21 mg/ml) were observed in the patients in contrast to control group. The reversal of antioxidants in later stages of CRC may be due to compensatory mechanisms in cancerous cells. The levels of MDA (nmol/ml) were also assessed, which shows significantly increased level in CRC patients as compared with control groups (3.67 ± 0.19 vs 1.31 ± 0.27). The levels of protein oxidation products [AGEs (2.74 ± 0.16 vs 0.84 ± 0.05 IU) and AOPPs (1.32 ± 0.02 vs 0.82 ± 0.07 ng/ml)] were significantly increased in subjects as compared with control. The levels of MMP-7 (64.75 ± 3.03 vs 50.61 ± 4.09 ng/ml) and isoprostanes (0.71 ± 0.03 vs 0.16 ± 0.02 ng/ml) were also analyzed. This shows that the levels of isoprostanes increased due to high lipid peroxidation mediate higher levels of MMP-7, which promotes development of CRC.ConclusionFollowing study suggested that elevated oxidative and inflammatory status along with lipid peroxidation and matrix metalloproteinases are the chief contributors in the progression of CRC.

ABSTRACT: BACKGROUND: Leukemia defined as the cancer of bone marrow i.e. leading to wild proliferation of blood forming cells. The WBCs are granulocytes, which avert bacterial infection and T and B lymphocytes. Prognostic measures for the disease are still not clear whereas, in children prognosis rate is better as compared to adults. MATERIALS AND METHODS: Fifty (n=50) patients of leukemia and fifty (n=50) were obtained and screened at Ganga Ram Hospital Lahore. Serum was separated and estimated for their 8hydroxy -2-deoxy guanosine, Isoprostanes, myeloperoxidase and cytokines such as TNF-α and several interleukins with their commercially available ELISA kits respectively. While neutrophils were estimated by the help of hematology analyzer and malondialdehyde (MDA) was estimatedby the method of Ohkawa. RESULTS: The results of the present study shows that variables of oxidative stressi.e., malondialdehyde (MDA), isoprostanes (IsoP-F2a), 8-hydroxy-2-deoxy guanosine (8-OHdG), neutrophils and cytokines including interleukin-6 (IL-6), tumor necrosis factor (TNF) and myeloperoxidase (MPO)differed significantly. The recorded levels of MDA (5.26±1.26 nmoles/ml), Isoprostanes (81.26±5.26 pg/ml), 8-OHdG (1.22±0.016 pg/ml), MPO (2.16±0.16 pg/ml) were significantly increased as compared to controls. Levels of cytokines i.e., IL-6 and TNF-α remained (6.59±2.16pg/ml) and (56.26±2.26 pg/ml) in diseased group while in controls they were(0.965±0.16pg/ml) and (0.15±0.015pg/ml)respectively. CONCLUSION: Performed research work concludes that leukemic patients have positive relation among disease progression and oxidative stress. It is characterized by increased the levels of oxidative stress markers significantly in serum concentration. Increased level of MDA signifies increased lipid peroxidation in the subjects of leukemic patients.

BACKGROUND:Chronic kidney disease (CKD) is a group of heterogeneous abnormalities affecting the function and structure of the kidney and mostly further proceeds to cardiovascular damage prior to end stage renal disease (ESRD). The oxidative insult and inflammatory mediators have some undefined role in CKD and cardiovascular complications. It is therefore, aimed at to pin point the predictive factors in the development of cardiovascular disorder in patients with chronic kidney disease. METHODS:Fifty patients of CKD experiencing cardiovascular distress and twenty normal individuals having same age and sex acted as control during these observations. Blood samples (Each 5 ml) were drawn and subjected to centrifugation for 10-15 minutes to separate the serum at 4000-5000rpm. The levels of MDA, GSH, SOD, CAT, VIT C, VIT E, IL-1, TNF-alpha, nitric oxide (NO) and advanced oxidation protein products (AOPPs) were estimated and analyzed. RESULTS:The nitric oxide levels in the CKD patients decreased significantly (13.26±1.25 ng/ml) compared to controls (42.15±5.26 ng/ml). The serum vitamin E and C levels in these patients recorded 2.15±0.25 μg/ml and 0.97±0.09 μg/ml respectively as against their assigned controls which read 6.35±1.22 μg/ml and 3.29±0.25 μg/ml. Furthermore, a significantly higher level of Malondialdehyde (MDA) as1.25±0.07 nmol/ml was observed in CKD patients viz-a-viz relevant control. However, the serum SOD, catalase (CAT) and GSH levels in the same patients registered a significant decline as evident from respective figures 0.07±0.002 μg/dl, 1.22±0.012 μmol/mol, and 3.25±1.05 μg/dl. The control for these was observed as0.99±0.06 μg/dl, 3.19±0.05 μmol/mol, and 8.64±0.03 μg/dL. On the other hand, the IL-1 levels in the CKD patients found quite higher (402.5±18.26 pg/ml). This clearly points to substantial increase in oxidative insult and reduced NO levels leading to the renal and cardiovascular damage. CONCLUSION:Observations support the fact that the decrease in anti-oxidative capacity accompanied by higher inflammatory mediators in CKD is indicative of oxidative stress, consequently leading to CKD progression, in all probability to cardiovascular insult. The outcome reiterates that strategies be designed afresh to contain CKD progression to cardiovascular complications and ESRD. One way could be to focus on early detection of stress related to the disease. It requires analyzing the factors related to stress, such as the one reported here. Linking these factors with the symptoms could be a crucial step forward. And further, the disease could be monitored in a more disciplined manner.

The metastasis of cancer epitomizes the diagnostic and therapeutic challenge as a result of cancer heterogeneity. To overcome the uncontrolled growth of the proliferating cells, nanosystems have been developed and have undergone many preclinical trials both in vitro and in vivo and many practices have been further applied clinically on human beings. In practice, magnetic nanoparticles- (MNPs-) based systems following the application of Fe3O4 bound antitumor drug have shown an enhanced therapeutic index in comparison with conventional chemotherapy ensuring the significant decline in nanosystems’ toxicity. A number of improved strategies employing nanoparticle engineering have been in practice for upgrading selectivity of metastatic cells and to have direct access to poorly manageable tumor regions. Targeted nanoparticle therapy paving the way towards tumor biomarkers and tissue specific cancer stages provides effective strategies for nonaccessible tumor regions, thus leading to the tangible modification in the history of cancer world. An infinite number of targets have been exploited for surface receptor specificity to distinct types of nanoparticles and are presently enduring clinical practices both in vitro and in vivo. The aim of this review is to take into view current nanotechnology-based research in cancer imaging for diagnosis and treatment. Several commercially available magnetic nanoparticles-based systems applied as contrast agents for metastatic cancer imaging and treatment via hyperthermia have also been focused on.

Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

Ovarian cancer is the 5th most common cause of deaths in the women among gynecological tumors. There are many growing evidences that stress and other behavioral factors may affect cancer progression and patient survival. The purpose of this study is to determine the key role of matrix metalloproteinases (MMPs), and cytokines in the aggregation and progression of ovarian cancer.Stress variables (MDA, AGEs, AOPPs, NO), profile of antioxidants (SOD, Catalase, Vitamin E & A, GSH, GRx, GPx) and inflammatory biomarkers (MMP-9, MMP-2, MMP-11, IL-1α and TNF-α) were biochemically assessed from venous blood of fifty ovarian cancer patients and twenty healthy control subjects. The results of all parameters were analyzed statistically by independent sample t-test.The results of the study demonstrated that the levels of stress variables like MDA (3.38±1.12nmol/ml), AGEs (2.72±0.22 ng/ml), AOPPs (128.48±27.23 ng/ml) and NO (58.71±8.67 ng/ml) were increased in the patients of ovarian cancer as compared to control individuals whereas the profile of antioxidants like SOD, Catalase, Vitamin E, Vitamin A, GSH and GRx were decreased in ovarian cancer patients (0.11±0.08 μg/ml, 2.41±1.01μmol/mol of protein, 0.22±0.04 μg/ml, 45.84±9.07μg/ml, 4.88±1.18μg/ml, 5.33±1.26 μmol/ml respectively). But the level of GPx antioxidant was increased in ovarian cancer patients (6.58±0.21μmol/ml). Moreover the levels of MMP-9 (64.87±5.35 ng/ml), MMP-2 (75.87±18.82 ng/ml) and MMP-11 (63.58±8.48 ng/ml) were elevated in the patients. Similarly, the levels of various cytokines TNF-α and IL-1α were also increased in the patients of ovarian cancer (32.17±3.52 pg/ml and 7.04±0.85 pg/ml respectively).MMPs are commonly expressed in ovarian cancer which are potential extrapolative biomarkers and have a major role in metastasis. Due to oxidative stress, different cytokines are released by tumor associated macrophages (TAMs) that result in the cancer progression. Consequently, tissue inhibitors of matrix metalloproteinases (TIMPs) are the valuable therapeutic approaches to complement conservative anticancer strategies.

Photovoltaics is the process of converting solar energy into electrical energy. Any photovoltaic system invariably consists of solar cell arrays and electric power conditioners. Photovoltaic systems are reliable, quiet, safe and both environmentally benign and self-sustaining. In addition, they are cost-effective for applications in remote areas. This paper presents a review of solar system components and integration, manufacturing, applications, and basic research related to photovoltaics. Photovoltaic applications in Oman are also presented. Finally, the existing and the future trends in technologies and materials used for the fabrication of solar cells are summarized.