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Any defects in bile formation, secretion, or flow may give rise to cholestasis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. As the pathogenesis of hepatic disorders is multifactorial, targeting parallel pathways potentially increases the outcome of therapy. Hypericum perforatum has been famed for its anti-depressive effects. However, according to traditional Persian medicine, it helps with jaundice and acts as a choleretic medication. Here, we will discuss the underlying molecular mechanisms of Hypericum for its use in hepatobiliary disorders. Differentially expressed genes retrieved from microarray data analysis upon treatment with safe doses of Hypericum extract and intersection with the genes involved in cholestasis are identified. Target genes are located mainly at the endomembrane system with integrin-binding ability. Activation of α5β1 integrins, as osmo-sensors in the liver, activates a non-receptor tyrosine kinase, c-SRC, which leads to the insertion of bile acid transporters into the canalicular membrane to trigger choleresis. Hypericum upregulates CDK6 that controls cell proliferation, compensating for the bile acid damage to hepatocytes. It induces ICAM1 to stimulate liver regeneration and regulates nischarin, a hepatoprotective receptor. The extract targets the expression of conserved oligomeric Golgi (COG) and facilitates the movement of bile acids toward the canalicular membrane via Golgi-derived vesicles. In addition, Hypericum induces SCP2, an intracellular cholesterol transporter, to maintain cholesterol homeostasis. We have also provided a comprehensive view of the target genes affected by Hypericum’s main metabolites, such as hypericin, hyperforin, quercitrin, isoquercitrin, quercetin, kaempferol, rutin, and p-coumaric acid to enlighten a new scope in the management of chronic liver disorders. Altogether, standard trials using Hypericum as a neo-adjuvant or second-line therapy in ursodeoxycholic-acid-non-responder patients define the future trajectories of cholestasis treatment with this product.

The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance is on the list of the top ten threats to global health. Immunomodulatory peptides that target a pathogen and modulate the immune system simultaneously are promising for the development of preventive and therapeutic molecules. Since investigating innate immunity in insects has led to prominent achievements in human immunology, such as toll-like receptor (TLR) discovery, we used the capacity of the immunomodulatory peptides of arthropods with concomitant antimicrobial or antitumor activity. An SVM-based machine learning classifier identified short immunomodulatory sequences encrypted in 643 antimicrobial peptides from 55 foe-to-friend arthropods. The critical features involved in efficacy and safety were calculated. Finally, 76 safe immunomodulators were identified. Then, molecular docking and simulation studies defined the target of the most optimal peptide ligands among all human cell-surface TLRs. SPalf2-453 from a crab is a cell-penetrating immunoadjuvant with antiviral properties. The peptide interacts with the TLR1/2 heterodimer. SBsib-711 from a blackfly is a TLR4/MD2 ligand used as a cancer vaccine immunoadjuvant. In addition, SBsib-711 binds CD47 and PD-L1 on tumor cells, which is applicable in cancer immunotherapy as a checkpoint inhibitor. MRh4-679 from a shrimp is a broad-spectrum or universal immunoadjuvant with a putative Th1/Th2-balanced response. We also implemented a pathway enrichment analysis to define fingerprints or immunological signatures for further in vitro and in vivo immunogenicity and reactogenicity measurements. Conclusively, combinatorial machine learning, molecular docking, and simulation studies, as well as systems biology, open a new opportunity for the discovery and development of multifunctional prophylactic and therapeutic lead peptides.

Medical trainees’ lifestyle has been changed particularly in the recent decade because of a group of health-related, social, and educational, variables. The emergence of COVID-19 and its effects on a wide variety of areas are such current cases. According to the published reports, the orientation of some changes has NOT been in support of healthier lifestyles (e.g., reduced interpersonal relationships, decrease in physical activity and so on).1, 2 Surely, as a warning and a matter of concern, such changes could affect our trainees’ qualifications regarding their professional performance. Academia provides an opportunity for performing developmental and/or preventive strategies that could help foster and maintain such qualifications in line with our social responsibility. Now, it seems that we require wise and in-time interventions- including but not limited to educational ones- for mediating side effects of the issue in the future. Despite its various dimensions, academic settings could responsibly approach this ongoing event through formal/informal curricula.

The use of functional foods (FFs) for maintaining health and preventing or treating illnesses—in recent years—has been dramatically increased in the literature. There are available valuable examples of FFs in ethno medicine from different tribes. Ethnic FFs can be valuable resources for developing FFs science, e.g., introducing memorial FFs as an interdisciplinary ethnopharmacological concept. In this paper, ethnic FFs from Bavi tribe (Kohgiluyeh va Boyerahmad province of Iran) have been studied, and their medical potentials are reported. Data gathering was done by interview with Bavi tribe local healers using a questionnaire. Plant materials were collected and identified, and Bavi FFs were prepared according to local procedures. Information of 21 Bavi tribe FFs was collected which are including 20 different plant species.The results showed that most FFs are used to treat chronic diseases including kidney problems like kidney stones, liver disease, neurological complaints, and GI ulcers and are used as lactogogue, while lesser FFs are used to treat acute diseases and symptoms (43%), including nausea and vomiting, common cold, diarrhea, sore throat, and allergy. Most FFs of Bavi tribe are prepared using aromatic plants (75%) responsible for aroma in the final FF. Probably, aromatic FFs increase patient acceptance, without mimicking unpleasant memory of drug recommendation. Plants that are used in FF are mostly perennial (80%) and wild growing (80%), indicating continuous contact of natives and so having memory with such habitant herbals. Treating diseases by homemade FFs which are prepared by well-known aromatic herbals is a routine procedure among natives like the Bavi tribe. Such easily made FFs with well-known taste and flavors which may change the patient’s mood should be studied in a new approach, “memorial FFs”, as a novel opportunity for healthcare and curing.

Familiarizing students with knowledge-based businesses is one of the goals emphasized in the developed educational systems worldwide. This study aimed to design a startup-based learning model (SBL). As a qualitative research study, startup teams were formed by the pharmacy students of Shiraz University of Medical Sciences in 2020. This model was used to train 120 students as pharmaceutical entrepreneurs through related lectures, simulations, and field activities. We employed this model for students to become familiar with the various stages of examining market needs, knowledge-based company registration, intellectual property, logo design, and even pharmaceutical product development. Students' feedback was assessed with a questionnaire designed by the team of researchers, and its results were used to analyze the course and improve the quality of the proposed model. Most of the studied indices revealed that the students rated this model as good or excellent. Satisfaction with more important indices includes student creativity and ideation in educational activity (60.7%), attractive presentation (60.4%), teamwork among learners (62.2%), appropriateness of evaluation method (65.4%), understanding how to make herbal remedies (49.1%), learner participation in the educational activity (74.8%), entrepreneurial motivation (60.7%), and applicability (64.4%). We found this model effective in boosting students' satisfaction, creativity, and entrepreneurial spirit. Lecturers also play a facilitator role in addition to specialized training. Therefore, in this model, both lecturers and students can grow more and make education more attractive. This study, for the first time, demonstrated that SBL could be applied in education systems and make the students more interested in educational content and help them to prepare for the job market.

The history of headache, as a common neurological complication, goes back to almost 9000 years ago. Many ancient civilizations present references to headaches and the coherent treatment strategies. Accordingly, several documents comprising headache complications embodying precise medical information stem from Traditional Persian Medicine (TPM) that can provide useful opportunities for more comprehensive treatment. We conducted a survey on headache through original important pharmacopeias and other important medical manuscripts of TPM which were written during 9 th to 19 th centuries and have derived all headache categories and herbal remedies. An extensive search of scientific data banks, such as Medline and Scopus, has also been exercised to find results relating to the anti-inflammatory, anti-nociceptive, and analgesic effects of denoted medicinal herbs. The concept of headache and treatments in TPM covers over 20 various types of headache and more than 160 different medicinal plants administered for oral, topical, and nasal application according to 1000 years of the subject documents. Nearly, 60% of remarked medicinal herbs have related anti-inflammatory or analgesic effects and some current headache types have similarities and conformities to those of traditional types. Beside historical approaches, there are many possible and available strategies that can lead to development of new and effective headache treatment from medicinal plants so that this study can provide beneficial information on clinical remedies based on centuries of experience in the field of headache which can stand as a new candidate for further investigations.

Antimicrobial peptides (AMPs) are the most favorable alternatives in overcoming multidrug resistance, alone or synergistically with conventional antibiotics. Plant-derived AMPs, as cysteine-rich peptides, widely compensate the pharmacokinetic drawbacks of peptide therapeutics. Compared to the putative genes encrypted in the genome, AMPs that are produced under stress are active forms with the ability to combat resistant microbial species. Within this study, plant-derived AMPs, namely, defensins, nodule-specific cysteine-rich peptides, snakins, lipid transfer proteins, hevein-like proteins, α-hairpinins, and aracins, expressed under biotic and abiotic stresses, are classified. We could observe that while α-hairpinins and snakins display a helix-turn-helix structure, conserved motif patterns such as β1αβ2β3 and β1β2β3 exist in plant defensins and hevein-like proteins, respectively. According to the co-expression data, several plant AMPs are expressed together to trigger synergistic effects with membrane disruption mechanisms such as toroidal pore, barrel-stave, and carpet models. The application of AMPs as an eco-friendly strategy in maintaining agricultural productivity through the development of transgenes and bio-pesticides is discussed. These AMPs can be consumed in packaging material, wound-dressing products, coating catheters, implants, and allergology. AMPs with cell-penetrating properties are verified for the clearance of intracellular pathogens. Finally, the dominant pharmacological activities of bioactive peptides derived from the gastrointestinal digestion of plant AMPs, namely, inhibitors of renin and angiotensin-converting enzymes, dipeptidyl peptidase IV and α-glucosidase inhibitors, antioxidants, anti-inflammatory, immunomodulating, and hypolipidemic peptides, are analyzed. Conclusively, as phytopathogens and human pathogens can be affected by plant-derived AMPs, they provide a bright perspective in agriculture, breeding, food, cosmetics, and pharmaceutical industries, translated as farm to bedside.

Rhubarb, the rhizome and root of Rheum palmatum L. from the Polygonaceae family, is a globally important medicinal plant, especially in eastern Asia. It has been indicated for enteritis, gastritis, constipation, and diarrhea in Persian medicine. Several pharmacological investigations in previous decades have been conducted on anthraquinones of rhubarb responsible for diarrheagenic activities and rhubarb tannins initiating anti-diarrheagenic effects. Aloe-emodin, chrysophanol, emodin, physcion, rhein, and their glycosides are major rhubarb anthraquinones. Moreover, catechin, catechin gallate, catechin-glucopyranoside, gallic acid, galloyl glucose, carboxyl-chrysophanol-O- glucose, coumaroyl-O-galloyl-glucose, di-O-galloyl-glucose, glucopyranosyl-galloyl-glucose, and di-, tri-, tetra-, and pentamer of catechin units are major rhubarb tannins. In this paper, a review of relevant pharmacological studies on rhubarb tannins and anthraquinones published in PubMed and Scopus databases is performed. In addition, the hub genes and common targets of rhubarb anthraquinones and tannins were investigated using gene expression databases. Thirty common differentially expressed target genes were identified. According to the survey, the pharmacology of rhubarb is linked to aquaporin expression and maintained inflammatory responses in the intestinal environment, where anthraquinones and tannins play as positive and negative regulators. Furthermore, their opposing effects on intestinal motility, fluid absorption, and water/electrolyte secretion are explained. Anthraquinones inhibit the Na + /K + ATPase pump while stimulating cystic fibrosis transmembrane conductance regulator (CFTR) and Ca 2+ -activated Cl − channels (CACC). Tannins reduce fluid secretion and smooth muscle contraction by inhibiting CACC and CFTR. This linkage opens new aspects for rhubarb pharmacology, its diarrheagenic/anti-diarrheagenic effects, and philosophical concepts of Hot and Cold temperaments in traditional medicine.

Any defects in bile formation, secretion, or flow may give rise to cholestasis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. As the pathogenesis of hepatic disorders is multifactorial, targeting parallel pathways potentially increases the outcome of therapy. Hypericum perforatum has been famed for its anti-depressive effects. However, according to traditional Persian medicine, it helps with jaundice and acts as a choleretic medication. Here, we will discuss the underlying molecular mechanisms of Hypericum for its use in hepatobiliary disorders. Differentially expressed genes retrieved from microarray data analysis upon treatment with safe doses of Hypericum extract and intersection with the genes involved in cholestasis are identified. Target genes are located mainly at the endomembrane system with integrin-binding ability. Activation of α5β1 integrins, as osmo-sensors in the liver, activates a non-receptor tyrosine kinase, c-SRC, which leads to the insertion of bile acid transporters into the canalicular membrane to trigger choleresis. Hypericum upregulates CDK6 that controls cell proliferation, compensating for the bile acid damage to hepatocytes. It induces ICAM1 to stimulate liver regeneration and regulates nischarin, a hepatoprotective receptor. The extract targets the expression of conserved oligomeric Golgi (COG) and facilitates the movement of bile acids toward the canalicular membrane via Golgi-derived vesicles. In addition, Hypericum induces SCP2, an intracellular cholesterol transporter, to maintain cholesterol homeostasis. We have also provided a comprehensive view of the target genes affected by Hypericum’s main metabolites, such as hypericin, hyperforin, quercitrin, isoquercitrin, quercetin, kaempferol, rutin, and p-coumaric acid to enlighten a new scope in the management of chronic liver disorders. Altogether, standard trials using Hypericum as a neo-adjuvant or second-line therapy in ursodeoxycholic-acid-non-responder patients define the future trajectories of cholestasis treatment with this product.