Argel's stemmoside C as a novel natural remedy for mice with alcohol-induced gastric ulcer based on its molecular mechanistic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Solenostemma argel is widely distributed in Africa & Asia with traditional usage in alleviating abdominal colic, aches, & cramps. This plant is rich in phytochemicals, which must be explored for its pharmacological effects. PURPOSE: Peptic Ulcer Disease (PUD) is the digestion of the digestive tube. PUD not only interferes with food digestion & nutrient absorption, damages one of the largest defensive barriers against pathogenic micro-organisms, but also impedes drug absorption & bioavailability, rendering the oral route, the most convenient way, ineffective. Omeprazole, one of the indispensable cost-effective proton-pump inhibitors (PPIs) extensively prescribed to control PUD, is showing growing apprehensions toward multiple drug interactions & side effects. Hence, finding a natural alternative with Omeprazole-like activity & limited side effects is a medical concern. STUDY DESIGN: Therefore, we present Stemmoside C as a new gastroprotective phytochemical agent isolated from Solenostemma argel to be tested in upgrading doses against ethanol-induced gastric ulcers in mice compared to negative, positive, & reference Omeprazole groups. METHODS: We carried out in-depth pharmacological & histopathological studies to determine the possible mechanistic pathway. RESULTS: Our results showed that Stemmoside C protected the stomach against ethanol-induced gastric ulcers parallel to Omeprazole. Furthermore, the mechanistic studies revealed that Stemmoside C produced its effect using an orchestrated array of different mechanisms. Stemmoside C stimulates stomach defense by increasing COX-2, PGE-2, NO, & TFF-1 healing factors, IL-10 anti-inflammatory cytokine, & Nrf-2 & HO-1 anti-oxidant pathways. It also suppresses stomach ulceration by inhibiting leucocyte recruitment, especially neutrophils, leading to subsequent inhibition of NF-κBp65, TNF-α, IL-1ß, & iNOS pro-inflammatory cytokines & JAK-1/STAT-3 inflammation-induced carcinogenicity cascade in addition to MMP-9 responsible for tissue degradation. CONCLUSION: These findings cast light on Stemmoside C's clinical application against gastric ulcer progression, recurrence, & tumorigenicity & concurrently with chemotherapy.

Arabincoside B isolated from Caralluma arabica as a potential anti-pneumonitis in LPS mice model.

Acute lung injury (ALI) is a life-threatening condition usually associated with poor therapeutic outcomes and a high mortality rate. Since 2019, the situation has worsened due to the COVID-19 pandemic. ALI had approximately 40% of deaths before COVID-19, mainly due to the dysfunction of the blood-gas barrier that led to lung edema, failure of gas exchange, and dyspnea. Many strategies have been taken to mitigate the disease condition, such as diuretics, surfactants, antioxidants, glucocorticoids, heparin, and ventilators with concomitant sedatives. However, until now, there is no available effective therapy for ALI. Thus, we are presenting a new compound termed Arabincoside B (AR-B), recently isolated from Caralluma arabica, to be tested in such conditions. For that, the lipopolysaccharide (LPS) mice model was used to investigate the capability of the AR-B compound to control the ALI compared to standard dexamethasone. The results showed that AR-B had a significant effect on retrieving ALI. A further mechanistic study carried out in the serum, lung homogenate, histological, and immunohistochemistry sections revealed that the AR-B either in 50 mg/kg or 75 mg/kg dose inhibited pro-inflammatory cytokines such as IL-6, IL-13, NF-κB, TNFα, and NO and stimulated regulatory cytokines IL-10. Moreover, AR-B showed a considerable potential to protect the pulmonary tissue against oxidative stress by decreasing MDA and increasing catalase and Nrf2. Also, the AR-B exhibited an anti-apoptotic effect on the lung epithelium, confirmed by reducing COX and BAX expression and upregulating Bcl-2 expression. These results pave its clinical application for ALI.

Ultrasonographic & biochemical analysis of thyroid bio-architecture for further pharmacological intervention in adult Arabian stallions & mares.

Based on the growing attention to the Arabian horses with a lack of records regarding their normal physiological parameters, which are critically vital for disease diagnosis &convenient drug administration, we give great attention to their thyroid gland normalcy. The thyroid gland is one of the key players in regulating many physiological processes. Therefore, we tackled thyroid biology & morphology in 14 Arabian stallions & 18 Arabian mares from the beginning of March to the middle of April on animals from 4 to 19 years old. First, the blood samples taken from their jugular vein were used for hematological profile, lipid profile, glucose-coagulation axis & thyroid profile. Moreover, thyroid gland dimensions & volume were estimated using ultrasonography. Noteworthy, Arabian mares have significantly higher MCH & relative eosinophils than Arabian stallions, while Arabian stallions have significantly higher glucose levels than Arabian Mares. Interestingly, this study found that Arabian horses have a high level of Total T4 & low level of platelets count compared to other horses. These results pointed to the deiodinase inhibitors as a possible target therapy for hyperthyroidism & thyroid cancer in Arabian horses, making surgery a second option. Also, these results refer to the caution required before giving Arabian horses high plasma protein bounded drugs, especially anticoagulants. Also, sonographic results showed that the left lobe is larger than the right lobe in both genders, & the lobes volume is larger in Arabian horses compared to others. These results would guide the veterinarian during diagnosis & thyroidectomy.

Evaluation of anti-Alzheimer activity of Echinacea purpurea extracts in aluminum chloride-induced neurotoxicity in rat model.

Alzheimer's disease (AD) is one of the neurodegenerative illnesses that impair individual life & increase the demand for caregivers with no available curative medication right now. Therefore, there is a growing concern about employing herbal medicine to limit AD progression & improve patients' life quality, thus potentiating its add-on therapy. In addition, herbs are cost-effective & accessible with nearly no side effects. In the same vein, our study aimed to investigate the potency of Echinacea purpurea (EP) flower extracts to ameliorate the neurodegenerative effect of Aluminum chloride (AlCl3) in a rat model. Moreover, mechanistic studies, including impact on the cholinesterase activity, redox status, inflammatory mediators, behavior performance, glucose level & histopathology, were carried on. Our results showed that 250 mg/kg of Aqueous (AQ) & Alcoholic (AL) extracts of EP inhibited cholinesterase, restored oxidative balance, down-regulated IL-6 & TNF-α cytokines & improved behavior performance in vivo that was reflected in the brain picture by decreasing neuronal degeneration & amyloid plaques in cerebral cortex & hippocampus. The potency of both extracts was compared to reference drugs & AlCl3 positive control group. The AQ extract showed greater potency against COX-1, COX-2 & α-amylase in vitro, while the AL extract was more potent against cholinesterase in vitro, inflammatory cytokines, behavior & pathological improvement in vivo. Conclusively EP overcame AlCl3-induced neurobehavioral toxicity in the rat model via different pathways, which support its regular administration to postpone progressive neural damage in AD patients.

CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer.

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15-20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution.

Nano-engineered delivery systems for cancer imaging and therapy: Recent advances, future direction and patent evaluation.

Cancer is the second highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small molecule inhibitors and nanotherapeutics have been employed in battling cancer. Amongst them, nanotheranostics is an example of successful personalized medicine bearing dual role of early diagnosis and therapy to cancer patients. In this review, we have focused on various types of theranostic polymer and metal nanoparticles for their role in cancer therapy and imaging concerning their limitation, future application such as dendritic cell cancer vaccination, gene delivery, T-cell activation and immune modulation. Also, some of the recorded patent applications and clinical trials have been illustrated. The impact of the biological microenvironment on the biodistribution and accumulation of nanoparticles have been discussed.

Multifunctional nanoparticles for cancer immunotherapy: A groundbreaking approach for reprogramming malfunctioned tumor environment.

Several cancer immunotherapy approaches have been recently introduced into the clinics and they have shown remarkable therapeutic potentials. The groundbreaking cancer immunotherapeutic agents function as a stimulant or modulator of the body immune system to fight against or kill cancers. Although targeted immunotherapies such as immune check point inhibitors (CTLA-4 or PD-1/PD-L1), DNA vaccination and CAR-T therapy are revolutionizing cancer treatment, the delivery efficacy can be further improved while their off-target toxicity can be mitigated through nanotechnology approaches. Recent research has demonstrated that nanotechnology has multifaceted role for (i) reeducating tumor associated macrophages (TAM) to function as tumor suppressor agent, (ii) serving as an efficient alternative for Chimeric Antigen Receptor (CAR)-T cell generation and transduction, and (iii) selective knockdown of Kras oncogene addiction by nano-Crisper-Cas9 delivery system. The function of host immune stimulatory signals and tumor immunotherapies can further be improved by repurposing of nanomedicine platform. This review summarizes the role of multifunctional polymeric, lipid, metallic and cell based nanoparticles for improving current immunotherapy.

Pharmacological Inhibitors of NAD Biosynthesis as Potential An ticancer Agents.

BACKGROUND: Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics through inhibition of cancer metabolism. Nicotinamide Adenine Dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer. OBJECTIVE AND METHOD: The main objective of this article is to review the recent patents which develop and implicate the chemical inhibitors of the key NAD+ biosynthetic enzymes for cancer treatment. We first discuss the biological principles of NAD+ metabolism in normal and malignant cells, with a focus on the feasibility of selectively targeting cancer cells by pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT) and indoleamine/tryptophan 2,3-dioxygenases (IDO/TDO), the rate-limiting salvage and de novo NAD+ biosynthetic enzymes, respectively. We then analyze a series of recent patents on development and optimization of chemical scaffolds for inhibiting NAMPT or IDO/TDO enzymes as potential anticancer drugs. Conclusion and Results: We have reviewed 16 relevant patents published since 2015, and summarized the chemical properties, mechanisms of action and proposed applications of the patented compounds. Without a better understanding of the properties of these compounds, their utility for further optimization and clinical use is unknown. For the compounds that have been tested using cell and mouse models of cancer, results look promising and clinical trials are currently ongoing to see if these results translate to improved cancer treatments.