Biotechnology
Role of Artificial Intelligence in Drug Discovery to Revolutionize the Pharmaceutical Industry: Resources, Methods and Applications
Traditional drug discovery methods such as wet-lab testing validations and synthetic techniques are time-consuming and expensive. Artificial Intelligence (AI) approaches have progressed to the point where they can have a significant impact on the drug discovery process. Using massive volumes of open data artificial intelligence methods are revolutionizing the pharmaceutical industry. In the last few decades many AI-based models have been developed and implemented in many areas of the drug development process. These models have been used as a supplement to conventional research to uncover superior pharmaceuticals expeditiously. AI's involvement in the pharmaceutical industry was used mostly for reverse engineering of existing patents and the invention of new synthesis pathways. Drug research and development to repurposing and productivity benefits in the pharmaceutical business through clinical trials. AI is studied in this article for its numerous potential uses. We have discussed how AI can be put to use in the pharmaceutical sector specifically for predicting a drug's toxicity bioactivity and physicochemical characteristics among other things. In this review article we have discussed its application to a variety of problems including de novo drug discovery target structure prediction interaction prediction and binding affinity prediction. AI for predicting drug interactions and nanomedicines were also considered.
Nutritional Health Connection of Algae and its Pharmaceutical Value as Anticancer and Antioxidant Constituents of Drugs
The marine environment is one of the major biomass producers of algae and seaweed; it is rich in functional ingredients or active metabolites with valuable nutritional health effects. Algal metabolites derived from the cultivation of both microalgae and macroalgae may positively impact human health offering physiological pharmaceutical and nutritional benefits. Microalgae have been widely used as novel sources of bioactive substances. Bioactive polymers extracted from algae such as algal fucans Galatians alginates phenolics carotenoids vitamin B12 and peptides possess antioxidant anticoagulant antimicrobial antiviral anti-inflammatory anti-allergy anticancer and hypocholesterolemic properties. It emphasizes that using marine-derived compounds with bioactive properties as functional food ingredients may help promote human health and prevent chronic diseases. Utilizing bioactive compounds has demonstrated notable advantages in terms of effectiveness more than conventional treatments and therapies currently in use which is also proven from different patents about algal applications in different fields. Despite the availability of numerous microalgae-derived products catering to human health and nutrition in the market there remains a lack of social acceptance and awareness regarding the health benefits of microalgae. Hence this review aims to offer a comprehensive account of the current knowledge on anticancers antioxidants commercially available edible algal products and therapeutics isolated from algae.
Medicinal Plants in the Treatment of Respiratory Diseases and their Future Aspects
The utilization of medicinal plants in the treatment of respiratory diseases has a rich history dating back centuries. A vast body of research literature including review articles research papers case studies patents and books provides substantial evidence supporting the use of medicinal plants in the treatment of diseases and injuries. This study delves into the diverse range of plant species known for their therapeutic properties with a specific focus on their applications in respiratory health. Medicinal plants have played a crucial role as a source of ingredients for medications and the synthesis of drugs. Globally over 35000 plant species are employed for medicinal purposes particularly in emerging countries where traditional medicine predominantly plant-based pharmaceuticals serves as a primary healthcare resource. This review highlights the significance of medicinal plants such as aloe ginger turmeric tulsi and neem in treating a wide array of common respiratory ailments. These plants contain bioactive compounds including tannins alkaloids sugars terpenoids steroids and flavonoids which have diverse therapeutic applications. Some medicinal plants notably Echinacea purpurea and Zingiber officinale exhibit potential for adjuvant symptomatic therapy in respiratory conditions such as chronic obstructive pulmonary disease (COPD) bronchitis asthma the common cold cough and whooping cough. The leaves of medicinal plants like Acacia torta Ocimum sanctum Mentha haplocalyx Lactuca virosa Convolvulus pluricaulis and Acalypha indica are commonly used to address pneumonia bronchitis asthma colds and cough. This review aims to shed light on specific medicinal plants with therapeutic value providing valuable insights for researchers in the field of herbal medicine. These plants hold the potential to serve as novel therapeutic agents in the treatment of respiratory diseases.
Construction of Camelus dromedaries Immune Single Domain Antibodies Library for Development of Schistosoma mansoni Specific Nanobodies using Phage Display Strategy
Schistosoma mansoni poses a considerable global public health challenge. In Egypt approximately 60% of the inhabitants in the Northern and Eastern areas of the Nile Delta are affected by this parasite whereas the Southern region experiences a significantly lower infection rate of 6%.
Construction of an immune phage display Nbs library based on the VHH framework for selecting S. mansoni-specific Nbs for seeking cost-effective sensitive and specific diagnostic tools for rapidly detecting Schistosoma mansoni.
Camel was immunized using soluble adult worm antigens (SAWP) for the production of Variable domains of heavy chains of camelid heavy-chain only antibodies (VHHs) which are known as nanobodies (Nb). The PBMCs repertoires VHH sequences library have been constructed with a high percentage of insertion and right orientation using pADL-23c phagmid and M13 phage followed by three rounds of bio-panning against SAWP using phage display technique. Evaluations using polyclonal phage ELISA and other techniques have been carried out to reveal the successful enrichment of anti-SAWP Nbs (VHH) clones. Evaluation of the diagnostic potentiality of these Nbs was carried out using ELISA on human serum samples confirmed for S. mansoni infection. Receiver Operator of Characteristics (ROC) curve analysis was used for discrimination between S. mansoni infection and both negative controls and the Fasciola hepatica group.
Using monoclonal ELISA Nbs of 22 clones out of 24 selected clones showed binding affinity to SAWP. The cutoff values of the produced anti-S. mansoni Nbs was > 0.19 leading to 80% sensitivity 95% specificity and 90% accuracy. Sequence analysis of three of these Nbs with high binding affinities showed diversity in their targets considering their CDR3 aa sequences.
This study successfully generated a diverse phage library enriched with anti-S. mansoni VHHs. The nanobodies produced exhibit high diagnostic potential for detecting S. mansoni infection in human patients offering a promising avenue for the development of efficient diagnostic tools. The innovative approach described herein may have potential applications for patent considerations in the field of the field of diagnostic technology.
Carvacrol: Innovative Synthesis Pathways and Overview of its Patented Applications
This research concerns the patentability of carvacrol; it could be helpful for researchers to easily identify any innovation in the biotechnological application of this monoterpene as well as other similar compounds.
Like thyme or oregano several plants in the Lamiaceae family produce carvacrol. It is one of the secondary metabolites with several biological activities including the improvement in plants’ resistance and their protection. Carvacrol has many chemical properties such as antioxidant and anti-microbial which have made it interesting for multiple biotechnological applications in the fields of food feed pharmacology and cosmetology.
We have made an attempt to demonstrate the value of carvacrol first by studying quantitative data from patent documents and then through some relevant patents we have tried to highlight the various fields of innovation related to the properties of carvacrol.
For the study we have collected and sorted patent documents (i.e. patent applications and granted patents) from specialized patent databases using “carvacrol” and some of its synonyms as keywords. The selected documents have included these keywords in their titles abstracts or claims. Then thanks to patent analysis we have tried to provide an overview of the useful properties of organic compounds.
We have shown that about 90% of the patent documents studied have been published in the 2000s. The number of publications which is constantly increasing demonstrates the growing interest in carvacrol. Although the applications of carvacrol are varied the data on the IPC classification show that most published innovations are concerned with formulations in the fields of health food and feed. The study of the most relevant patents has allowed us to highlight some developments in the extraction and synthesis of carvacrol and some examples of patents that illustrate the wide possibilities offered by the exploitation of carvacrol. Thus we have discussed its use in the cosmetic pharmaceutical food and agricultural fields.
Carvacrol is a natural compound with beneficial properties. Several applications using this monoterpene have already been patented in different fields. However the evolution of patentability has grown this past year and revealed the potential of carvacrol in biotechnology.
The Role of NAD+ in Myocardial Ischemia-induced Heart Failure in Sprague-dawley Rats and Beagles
Introduction: Nicotinamide adenine dinucleotide (NAD+) participates in various processes that are dysregulated in cardiovascular diseases. Supplementation with NAD+ may be cardioprotective. However whether the protective effect exerted by NAD+ in heart failure (HF) is more effective before acute myocardial infarction (MI) or after remains unclear. The left anterior descending arteries of male Sprague Dawley rats and beagles that developed HF following MI were ligated for 1 week following which the animals were treated for 4 weeks with low medium and high doses of NAD+ and LCZ696. Methods: Cardiac function hemodynamics and biomarkers were evaluated during the treatment period. Heart weight myocardial fibrosis and MI rate were measured eventually. Results: Compared with the HF groups groups treated with LCZ696 and different doses of NAD+ showed increased ejection fractions fractional shortening cardiac output and stroke volume and decreased end-systolic volume end-systolic dimension creatine kinase and lactic dehydrogenase. LV blood pressure was lower in the HF group than in the control group but this decrease was significantly greater in the medium and high NAD+ dose groups. Conclusion: The ratios of heart weight indexes fibrotic areas and MI rates in the CZ696 and medium and high NAD+ dose groups were lower than those in the HF group. Medium and highdose NAD+ showed superior positive effects on myocardial hypertrophy cardiac function and myocardial fibrosis and reduced the MI rate.
An Updated Review on Nanoemulsion: Factory for Food and Drug Delivery
Background: A nanoemulsion is a colloidal system of small droplets dispersed in another liquid. It has attracted considerable attention due to its unique properties and various applications. Throughout this review we provide an overview of nanoemulsions and how they can be applied to various applications such as drug delivery food applications and pesticide formulations. Objective: This updated review aims to comprehensively overview nanoemulsions and their applications as a versatile platform for drug delivery food applications and pesticide formulations. Methods: Research relevant scientific literature across various databases including PubMed Scopus and Web of Science. Suitable keywords for this purpose include "nanoemulsion" "drug delivery" and "food applications." Ensure the search criteria include recent publications to ensure current knowledge is included. Results: Several benefits have been demonstrated in the delivery of drugs using nanoemulsions including improved solubility increased bioavailability and controlled delivery. Nanoemulsions have improved some bioactive compounds in food applications including vitamins and antioxidants. At the same time pesticide formulations based on nanoemulsions have also improved solubility shelf life and effectiveness. Conclusion: The versatility of nanoemulsions makes them ideal for drug delivery food and pesticide formulation applications. These products are highly soluble bioavailable and targeted providing significant advantages. More research and development are required to implement nanoemulsion-based products on a commercial scale.
Diagnosis of Canine Visceral Leishmaniasis by Flow Cytometry Serology using the rMELEISH Multiepitope Antigen Coupled in a Functional Bead
Background: Visceral leishmaniasis (VL) is a zoonotic disease with dogs being the main reservoir of the Leishmania infantum parasite. Objective: To develop a new flow cytometry test to diagnosis canine VL (CVL) diagnosis. Methods: The current study addresses a new flow cytometry test using beads coupled to the multiepitope antigen rMELEISH. Results: In the study set of samples a sensitivity (87.1%) and specificity (89.9%) was observed. Considering the dogs’ clinical status 20/20 (100.0%) of the symptomatic sera tested positive while 19/22 (86.4%) of the oligosymptomatic and 16/20 (80.0%) of asymptomatic were positive. In the non-infected control all samples (0/30) tested as negative. In the cross-reaction control the test was more efficient in dogs infected with L. braziliensis (2/10) and Trypanosoma cruzi (0/10) than those with Babesia canis (4/10) and Ehrlichia canis (4/10). Dogs immunized with different vaccines (Leishmune Leish-Tec® or LBSap) did not present serological reactivity. Conclusion: The flow cytometry serology through coupling the antigen rMELEISH in functional beads showed high accuracy in diagnosing CVL.
Acknowledgement to Reviewers
Oleogels for the Promotion of Healthy Skin Care Products: Synthesis and Characterization of Allantoin Containing Moringa-based Oleogel
Background: Oleogelation is an efficient and emerging approach for obtaining biocompatible and biodegradable elastic semisolid crystals to be used in various cosmetic and pharmaceutical formulations. Recently drug incorporation in oil structuring has been a promising strategy under consideration due to the effectiveness of this method. Plant oils have very beneficial characteristics for skin care and wound healing due to the presence of certain antioxidants. Methods: In this study the oleogels of Moringa oleifera seed oil with natural polysaccharides including pectin chitosan and xanthan gum were prepared using the emulsion template method. Moringa oil was selected because it can hydrate and moisturize the skin and has great antioxidant activity. Also the natural polysaccharides i.e. pectin and chitosan exhibited good gelling properties. Allantoin which is a wound healer and eucalyptus leaf oil with antioxidant potential was incorporated into the emulsion-based-oleogels to enhance the antioxidant and antimicrobial activity of the oleogels. Results: Allantoin and eucalyptus-loaded oleogels exhibited good antibacterial activity against E. coli. The FTIR spectra of moringa-based oleogels in the range between 3226-3422 cm-1 indicate the presence of hydrogen bonding in oleogels. Conclusion: The antioxidant potential of allantoin and eucalyptus-containing oleogel was maximized and an IC50 value of 0.9719 μM was found. Maximum release of allantoin from oleogel was observed in the first hour.
The Use of Lipid-based Nanocarriers to Improve Ovarian Cancer Treatment: An Overview of Recent Developments
Ovarian cancer poses a formidable health challenge for women globally necessitating innovative therapeutic approaches. This review provides a succinct summary of the current research status on lipid-based nanocarriers in the context of ovarian cancer treatment. Lipid-based nanocarriers including liposomes solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) offer a promising solution for delivering anticancer drugs with enhanced therapeutic effectiveness and reduced adverse effects. Their versatility in transporting both hydrophobic and hydrophilic medications makes them well-suited for a diverse range of anticancer drugs. Active targeting techniques like ligand-conjugation and surface modifications have been used to reduce off-target effects and achieve tumour-specific medication delivery. The study explores formulation techniques and adjustments meant to enhance drug stability and encapsulation in these nanocarriers. Encouraging results from clinical trials and preclinical investigations underscore the promise of lipid-based nanocarriers in ovarian cancer treatment providing optimism for improved patient outcomes. Notwithstanding these advancements challenges related to clearance long-term stability and scalable manufacturing persist. Successfully translating lipidbased nanocarriers into clinical practice requires addressing these hurdles. To sum up lipidbased nanocarriers are a viable strategy to improve the effectiveness of therapy for ovarian cancer. With their more focused medication administration and lower systemic toxicity they may completely change the way ovarian cancer is treated and increase patient survival rates. Lipidbased nanocarriers need to be further researched and developed to become a therapeutically viable treatment for ovarian cancer.
Icariin Attenuates Human Renal Tubular Epithelial Cell Senescence by Targeting PAK2 via miR-23b-3p
Background: Renal tubular epithelial cells (RTECs) senescence is crucial in kidney diseases. Icariin is shown to have protective effects against renal fibrosis acute kidney injury and proteinuria. We aimed to explore the role of icariin in protecting RTECs from senescence and the underlying mechanism involved. Methods: An in vitro model of RTEC senescence was established by incubating HK-2 cells with urine exosomes from patients with diabetic kidney disease. Stimulated cells were treated with icariin at various doses to evaluate the compound's therapeutic effects. After RNA transfection cell cycle arrest and senescence flow cytometry and SA-β-Gal staining were analyzed. At the same time quantitative real-time PCR examined microRNA expression. Biochemical assays. Results: Urine exosomes induced senescence and cell cycle arrest in the G1 stage in HK-2 cells which were inhibited by icariin. Urine exosome stimulation up-regulated miR-23b-3p expression which in turn suppressed PAK2 expression. Significantly the induced and inhibited miR- 23b-3p expressions weakened and augmented the resistance of cells against urine exosome stimulation respectively while PAK2 overexpression provided additional protection. Icariin suppressed miR-23b-3p expression and miR-23b-3p induction blocked the effects of icariin and promoted RTEC senescence. Conclusion: miR-23b-3p and PAK2 form a signaling axis that regulates RTEC senescence upon urine exosome stimulation. Icariin can increase the resistance of RTECs against senescence via miR-23b-3p/PAK2. Our findings shed light on the mechanism of the clinical effects of icariin on renal diseases which can be exploited to develop effective drugs targeting RTEC senescence in the future.
Traditional Chinese Medicine-based Treatment in Cardiovascular Disease: Potential Mechanisms of Action
Cardiovascular Disease (CVD) is the leading cause of morbidity and death worldwide and has become a global public health problem. Traditional Chinese medicine (TCM) has been used in China to treat CVD and achieved promising results. Therefore TCM has aroused significant interest among pharmacologists and medical practitioners. Previous research showed that TCM can regulate the occurrence and development of atherosclerosis (AS) ischemic heart disease heart failure myocardial injury and myocardial fibrosis by inhibiting vascular endothelial injury inflammation oxidant stress ischemia-reperfusion injury and myocardial remodeling. It is well-known that TCM has the characteristics of multi-component multi-pathway and multitarget. Here we systematically review the bioactive components pharmacological effects and clinical application of TCM in preventing and treating CVD.
Role of Protein Ubiquitination and HIF Signaling in the Evolution of Hypoxic Breast Cancer
Alternations in protein ubiquitination along with hypoxia-inducible factor (HIF) signaling contribute to tumorigenesis and breast tumor advancement. Ubiquitination is an impulsive process which is coordinately governed by E3 ligases and deubiquitinases (DUBs) that have come out as charismatic therapeutic targets. HIF expression as well as the transcriptional process in malignancies are frequently elevated resulting in pitiable clinical outcomes. According to increasing research multiple E3 ligases in addition to UBDs work together to modulate HIF expression and activity permitting breast cancer cells to make out a hypoxic milieu. On the other hand hypoxia and HIF signaling regulate numerous E3 ligases as well as DUBs. Interpreting involved networks connecting E3 ligase DUBS and HIF will reveal profound mechanisms of physiological response to hypoxia and aid in the discovery of new molecular references for cancer management. The present state of knowledge about the entire kinship among E3 ligase DUBs and HIF signaling is reviewed here emphasizing using E3 ligase or DUB inhibitors in breast cancer.
Determination of Ideal Factors for Early Adoption and Standardization of Metagenomic Next-generation Sequencing for Respiratory System Infections
Background: Metagenomic next-generation sequencing (mNGS) demonstrates great promise as a diagnostic tool for determining the cause of pathogenic infections. The standard diagnostic procedures (SDP) include smears and cultures and are typically viewed as less sensitive and more time-consuming when compared to mNGS. There are concerns about the logistics and ease of transition from SDP to mNGS. mNGS lacks standardization of collection processes databases and sequencing. Additionally there is the burden of training clinicians on interpreting mNGS results. Objective: Until now few studies have explored factors that could be used as early adoption candidates to ease the transition between SDP and mNGS. This study evaluated 123 patients who had received both SDP and mNGS and compared several variables across a diagnostic test evaluation. Methods: The diagnostic test evaluation observed metrics such as sensitivity specificity positive and negative likelihood ratios (PLR NLR) positive and negative predictive values (PPV NPV) and accuracy. Factors included various sample sources such as bronchoalveolar lavage fluid (BALF) lung tissue and cerebral spinal fluid (CSF). An additional factor observed was the patient's immune status. Results: Pathogen detection was found to be significantly greater for mNGS for total patients BALF sample source CSF sample source and non-immunocompromised patients (p<0.05). Pathogen detection was found to be insignificant for lung tissue sample sources and immunocompromised patients. Sensitivity PLR NLR PPV NPV and accuracy appeared to be higher with mNGS for the total patients BALF sample source and non-immunocompromised patients when compared with SDP (p<0.05). Conclusion: With higher metrics in sensitivity specificity PLR NLR PPV NPV and accuracy for overall patients mNGS may prove a better diagnostic tool than SDP. When addressing sample sources mNGS for BALF-collected samples appeared to have higher scores than SDP for the same metrics. When patients were in a non-immunocompromised state mNGS also demonstrated greater diagnostic benefits to BALF and overall patients compared to SDP. This study demonstrates that using BALF as a sample source and selecting non-immunocompromised patients may prove beneficial as early adoption factors for mNGS standard protocol. Such a study may pave the road for mNGS as a routine clinical method for determining the exact pathogenic etiology of lung infections.
Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review
Background: Epilepsy is one of the most common in all age groups and disabling neurologic disorders around the world. Objectives: This systematic review was to explore whether berberine (BBR) has any anti-seizure or anti-epileptic effects and also reviewed this possible mechanism. Methods: The EMBASE Scopus Cochrane Library PubMed and Web of Science databases were searched before Sep 2023. All types of studies that investigated the effects of BBR on epilepsy or chemical-induced seizures were eligible for inclusion. Two authors independently evaluated and reviewed titles/abstracts to identify publications for potential eligibility and a third team member resolved discrepancies. Data were extracted in an Excel form and the outcomes were discussed. Results: BBR showed its neuroprotective properties by reducing oxidative stress neuroinflammation and anti-apoptosis effects. It also increases brain-derived neurotrophic factor (BDNF) release and reduces transforming growth factor-beta (TGF-β1) and hypoxia-inducible factor 1α (HIF-1α). BBR by increasing scavenging reactive oxygen species (ROS) nuclear factor erythroid 2–related factor 2 (Nrf2) endogenous antioxidant enzymes heme oxygenase-1 (HO-1) and inhibition of lipid peroxidation insert its antioxidant activity. Moreover BBR showed antiinflammatory activity by reducing Interleukin (IL)-1β IL-6 and tumor necrosis factor-alpha (TNF-α) levels and through inhibiting cyclooxygenase-2 (COX-2) and including nuclear factor ΚB (NF-ΚB). In addition it modulated c-fos expression and neuronal excitability in the brain. Conclusion: BBR indicated promising anti-seizure effects with remarkable antioxidant antiinflammatory anti-apoptotic and neuroprotective activity. Future studies should be based on well-designed clinical trial studies that are integrated with new methods related to increasing bioavailability.
Implementation of Silver Nanoparticles Green Synthesized with Leaf Extract of Coccinia grandis as Antimicrobial Agents Against Head and Neck Infection MDR Pathogens
Background: Head and neck infections (HNI) associated with multidrug resistance (MDR) offer several health issues on a global scale due to inaccurate diagnosis. Objectives: This study aimed to identify the bacteria and Candidal isolates and implement the silver nanoparticles green synthesized with leaf extract of Coccinia grandis (Cg-AgNPs) as a therapeutic approach against HNI pathogens. Methods: The Cg-AgNPs were characterized by the UV-visible spectrophotometer FT-IR analysis Zeta particle size Zeta potential and field emission scanning electron microscope (FESEM) analysis to validate the synthesis of nanoparticles. Additionally the antimicrobial activity of Cg-AgNPs was presented by the zone of inhibition (ZOI) minimum inhibitory concentration (MIC) minimum bactericidal/fungicidal concentration (MBC/MFC) and antibiofilm assay. Moreover the cell wall rupture assay was visualized on SEM for the morphological study of antimicrobial activities and the in-vivo toxicity was performed in a swiss mice model to evaluate the impact of Cg-AgNPs on various biological parameters. Results: Different bacterial strains (Staphylococcus aureus Acinetobacter baumannii Klebsiella pneumoniae and Pseudomonas aeruginosa) and Candida sp. (Candida albicans Candida tropicalis Candida orthopsilosis and Candida glabrata) were identified. The MIC MBC and antibiofilm potential of Cg-AgNPs were found to be highest against A. baumannii: 1.25 μg/ml 5 μg/ml and 85.01±5.19% respectively. However C. albicans and C. orthopsilosis revealed 23 mm and 21 mm of ZOI. Subsequently the micromorphology of the cell wall rupture assay confirmed the efficacy of Cg-AgNPs and no significant alterations were seen in biochemical and hematological parameters on the swiss mice model in both acute and subacute toxicity studies. Conclusion: The green synthesized Cg-AgNPs have multifunctional activities like antibacterial anticandidal and antibiofilm activity with no toxicity and can be introduced against the HNI pathogens.
The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies
Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review we have presented an overview of the bidirectional relationship between gut microbiota and MDD and the effect of pre-treatments and microbiomebased approaches such as probiotics prebiotics synbiotics fecal microbiota transplantation and a new generation of microbial alternatives on the improvement of unstable clinical conditions caused by MDD.