Current Pharmaceutical Biotechnology - Current Issue

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.