Bioconjugates: A New Class of Therapeutics for Cancer Treatment

مثل المرافقات الحيوية فئة جديدة من العلاجات التي تبشر بالخير في علاج السرطان. تتشكل هذه المركبات من خلال الجمع بين جزيء استهداف ، مثل الجسم المضاد أو الببتيد ، مع عامل علاجي ، مثل عقار العلاج الكيميائي أو السم. يسمح هذا النهج بالتسليم المستهدف للعامل العلاجي للخلايا السرطانية ، وتقليل الأضرار التي تلحق بالأنسجة السليمة وتقليل الآثار الجانبية. أظهرت المقارنات الحيوية إمكانات كبيرة في الدراسات قبل السريرية والسريرية ، مع العديد من الأدوية المعتمدة من إدارة الغذاء والدواء والمتاحة حاليًا لعلاج السرطان. هناك عدة أنواع من المركبات الحيوية التي يتم تطويرها حاليًا لعلاج السرطان ، بما في ذلك اتحادات الأدوية والأجسام المضادة ADCs، وتقارنات العقاقير الببتيدية PDCs، واتحادات الجسيمات النانوية (NDCs). ADCs هي أكثر أنواع المركبات الحيوية ترسخًا وقد تمت الموافقة عليها لعلاج عدة أنواع من السرطان ، بما في ذلك سرطان الثدي وسرطان الغدد الليمفاوية وسرطان الدم. PDCs و NDCs هي فئات جديدة من المركبات الحيوية التي لا تزال في مراحل التطور السريرية قبل السريرية والمبكرة. تهدف الأبحاث الجارية في هذا المجال إلى تحسين فعالية وسلامة المركبات الحيوية وتوسيع استخدامها لتشمل مجموعة واسعة من أنواع السرطان. مع استمرار تقدم البحث في هذا المجال ، يمكننا أن نتوقع رؤية المزيد من العقاقير الموصلة بيولوجيًا المبتكرة والفعالة التي يتم تطويرها في المستقبل. تم تصميم هذه الأدوية لاستهداف خلايا سرطانية معينة ، مع ترك الخلايا السليمة دون أن تصاب بأذى ، ولديها القدرة على إحداث ثورة في علاج السرطان. علاوة على ذلك ، يمكن تصميم المقارنات الحيوية لتناسب المرضى الفرديين ، مما يسمح بعلاج السرطان المخصص والموجه. مثل المرافقات الحيوية فئة جديدة من العلاجات التي تبشر بالخير في علاج السرطان. تتشكل هذه المركبات من خلال الجمع بين جزيء استهداف ، مثل الجسم المضاد أو الببتيد ، مع عامل علاجي ، مثل عقار العلاج الكيميائي أو السم. يسمح هذا النهج بالتسليم المستهدف للعامل العلاجي للخلايا السرطانية ، وتقليل الأضرار التي تلحق بالأنسجة السليمة وتقليل الآثار الجانبية. أظهرت المقارنات الحيوية إمكانات كبيرة في الدراسات قبل السريرية والسريرية ، مع العديد من الأدوية المعتمدة من إدارة الغذاء والدواء والمتاحة حاليًا لعلاج السرطان. هناك عدة أنواع من المركبات الحيوية التي يتم تطويرها حاليًا لعلاج السرطان ، بما في ذلك اتحادات الأدوية والأجسام المضادة ADCs، وتقارنات العقاقير الببتيدية PDCs، واتحادات الجسيمات النانوية (NDCs). ADCs هي أكثر أنواع المركبات الحيوية ترسخًا وقد تمت الموافقة عليها لعلاج عدة أنواع من السرطان ، بما في ذلك سرطان الثدي وسرطان الغدد الليمفاوية وسرطان الدم. PDCs و NDCs هي فئات جديدة من المركبات الحيوية التي لا تزال في مراحل التطور السريرية قبل السريرية والمبكرة. تهدف الأبحاث الجارية في هذا المجال إلى تحسين فعالية وسلامة المركبات الحيوية وتوسيع استخدامها لتشمل مجموعة واسعة من أنواع السرطان. مع استمرار تقدم البحث في هذا المجال ، يمكننا أن نتوقع رؤية المزيد من العقاقير الموصلة بيولوجيًا المبتكرة والفعالة التي يتم تطويرها في المستقبل. تم تصميم هذه الأدوية لاستهداف خلايا سرطانية معينة ، مع ترك الخلايا السليمة دون أن تصاب بأذى ، ولديها القدرة على إحداث ثورة في علاج السرطان. علاوة على ذلك ، يمكن تصميم المقارنات الحيوية لتناسب المرضى الفرديين ، مما يسمح بعلاج السرطان المخصص والموجه.Bioconjugates represent a novel class of therapeutics that offer promise in the treatment of cancer. These compounds are formed by combining a targeting molecule, such as an antibody or peptide, with a therapeutic agent, such as a chemotherapy drug or toxin. This approach allows for targeted delivery of the therapeutic agent to cancer cells, minimizing damage to healthy tissues and reducing side effects. Bioconjugates have shown significant potential in preclinical and clinical studies, with several FDA-approved drugs currently available for the treatment of cancer. There are several types of bioconjugates currently being developed for cancer treatment, including antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), and nanoparticle-drug conjugates (NDCs). ADCs are the most well-established type of bioconjugate and have been approved for the treatment of several types of cancer, including breast cancer, lymphoma, and leukemia. PDCs and NDCs are newer classes of bioconjugates that are still in the preclinical and early clinical stages of development. Ongoing research in this field aims to improve the efficacy and safety of bioconjugates and expand their use to a wider range of cancer types. As research in this field continues to advance, we can expect to see even more innovative and effective bioconjugate drugs being developed in the future. These drugs are designed to target specific cancer cells, while leaving healthy cells unharmed, and have the potential to revolutionize cancer treatment. Furthermore, bioconjugates can be tailored to individual patients, allowing for personalized and targeted cancer therapy. &nbsp

Genome-Wide Diversity of MADS-Box Genes in Bread Wheat is Associated with its Rapid Global Adaptability

MADS-box gene family members play multifarious roles in regulating the growth and development of crop plants and hold enormous promise for bolstering grain yield potential under changing global environments. Bread wheat (Triticum aestivum L.) is a key stable food crop around the globe. Until now, the available information concerning MADS-box genes in the wheat genome has been insufficient. Here, a comprehensive genome-wide analysis identified 300 high confidence MADS-box genes from the publicly available reference genome of wheat. Comparative phylogenetic analyses with Arabidopsis and rice MADS-box genes classified the wheat genes into 16 distinct subfamilies. Gene duplications were mainly identified in subfamilies containing unbalanced homeologs, pointing towards a potential mechanism for gene family expansion. Moreover, a more rapid evolution was inferred for M-type genes, as compared with MIKC-type genes, indicating their significance in understanding the evolutionary history of the wheat genome. We speculate that subfamily-specific distal telomeric duplications in unbalanced homeologs facilitate the rapid adaptation of wheat to changing environments. Furthermore, our in-silico expression data strongly proposed MADS-box genes as active guardians of plants against pathogen insurgency and harsh environmental conditions. In conclusion, we provide an entire complement of MADS-box genes identified in the wheat genome that could accelerate functional genomics efforts and possibly facilitate bridging gaps between genotype-to-phenotype relationships through fine-tuning of agronomically important traits

Wheat in the Era of Genomics and Transgenics

Wheat, as one of the most important cereal crops in the world and second major caloric source in the world after rice, is the major staple food in South Asia and many other countries of the world. Prior to onset of “Green Revolution,” South Asian countries were facing the threat of severe famine. Green Revolution wheat genotypes brought out these countries from the crisis they were facing and has helped them to sustain their productions for more than half a century. With the emergence of molecular biology and biotechnology, another window of opportunity is opened to sustain wheat yields by using modern techniques of genes identification and utilization. Through this chapter, we have tried to gather information that was generated for wheat improvement in last 3 decades. These afforest included the development of molecular markers, mapping of genes, sequencing of markers genes, and their utilization through marker-assisted selection. The other part recorded various efforts to genetically transform wheat for traits improvements and/or to study their molecular control

A rare presentation of acute flaccid myelitis in covid-19 patient: a case report

SARS-CoV-2 virus enters human cells via ACE-2 receptors and causes multiple organs dysfunction. These ACE-2 receptors are in cells surface of human lung, liver, heart, kidney and blood vessels. The expression of ACE2 receptors in cortical neurons, glial cells and spinal cord cells create nervous system susceptible to SARS-CoV-2 attack and may be a source of different neurological deficits including myelitis in COVID-19 patients

Climate Change and Citrus

Climate change is the change in the statistical distribution of weather patterns that lasts for an extended period. Climate change and agriculture are interrelated processes and affect in many ways. Citrus fruits are one of the largest fruit crops in the world. Yield loss at a drastic level due to abiotic stress annually in which temperature and water stress are the main environmental factors. These factors cause biochemical, anatomical, physiological, and genetic changes in plant structure and lead to defective growth, development, and reproduction, which ultimately cause a reduction in the economic yield of the crop. An increase in temperature and water stress at critical phenological stages of citrus results in reduced tree fruit set, decrease in fruit growth and size, increase in fruit acidity, low tree yield, reduced fruit peel thickness, and pre-harvest fruit drop. Stomatal conductance and net carbon dioxide assimilation in citrus leaves can be reduced by super optimal leaf temperature. Water deficit reduces the transpiration rate, stomatal conductance by stomatal closure associated with ABA content and causes an abrupt decrease in photosynthesis and CO2 assimilation in citrus which reduce trees overall growth and production. Interventions in agronomic practices, breeding strategies, and biotechnological approaches can mitigate climate change effects on citrus. The groundwork against climate change is compulsory for better global livelihood and food security

Phytochemical Analysis, Antioxidant, and Antimicrobial Activities of Ducrosia flabellifolia: A Combined Experimental and Computational Approaches

Ducrosia flabellifolia Boiss. is a rare desert plant known to be a promising source of bioactive compounds. In this paper, we report for the first time the phytochemical composition and biological activities of D. flabellifolia hydroalcoholic extract by using liquid chromatography-electrospray tandem mass spectrometry (ESI-MS/MS) technique. The results obtained showed the richness of the tested extract in phenols, tannins, and flavonoids. Twenty-three phytoconstituents were identified, represented mainly by chlorogenic acid, followed by ferulic acid, caffeic acid, and sinapic acid. The tested hydroalcoholic extract was able to inhibit the growth of all tested bacteria and yeast on agar Petri dishes at 3 mg/disc with mean growth inhibition zone ranging from 8.00 ± 0.00 mm for Enterococcus cloacae (E. cloacae) to 36.33 ± 0.58 mm for Staphylococcus epidermidis. Minimal inhibitory concentration ranged from 12.5 mg/mL to 200 mg/mL and the hydroalcoholic extract from D. flabellifolia exhibited a bacteriostatic and fungistatic character. In addition, D. flabellifolia hydroalcoholic extract possessed a good ability to scavenge different free radicals as compared to standard molecules. Molecular docking studies on the identified phyto-compounds in bacterial, fungal, and human peroxiredoxin 5 receptors were performed to corroborate the in vitro results, which revealed good binding profiles on the examined protein targets. A standard atomistic 100 ns dynamic simulation investigation was used to further evaluate the interaction stability of the promising phytocompounds, and the results showed conformational stability in the binding cavity. The obtained results highlighted the medicinal use of D. flabellifolia as source of bioactive compounds, as antioxidant, antibacterial, and antifungal agent

Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids

Therapeutic Outcomes of Isatin and Its Derivatives against Multiple Diseases: Recent Developments in Drug Discovery

Isatin (1H indole 2, 3-dione) is a heterocyclic, endogenous lead molecule recognized in humans and different plants. The isatin nucleus and its derivatives are owed the attention of researchers due to their diverse pharmacological activities such as anticancer, anti-TB, antifungal, antimicrobial, antioxidant, anti-inflammatory, anticonvulsant, anti-HIV, and so on. Many research chemists take advantage of the gentle structure of isatins, such as NH at position 1 and carbonyl functions at positions 2 and 3, for designing biologically active analogues via different approaches. Literature surveys based on reported preclinical, clinical, and patented details confirm the multitarget profile of isatin analogues and thus their importance in the field of medicinal chemistry as a potent chemotherapeutic agent. This review represents the recent development of isatin analogues possessing potential pharmacological action in the years 2016–2020. The structure–activity relationship is also discussed to provide a pharmacophoric pattern that may contribute in the future to the design and synthesis of potent and less toxic therapeutics

Kinetics of Anation of Hexaaquochromium(III) Ion by Valine in Aqueous Acidic Medium

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Kinetics of Anation of Hexaaquochromium(III) Ion by Serine in Aqueous-Acidic Medium

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