bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence-Based Prioritization and Scoring of Genomic Loci Interacting with Pioglitazone Therapeutic Response in Diabetic Patients.
Authors: Anum  , Imran Amirzada Muhammad , Uddin Zia , Muhammad Ikram  , Shah Abdul Jabbar , Shah Nabi 
Published: May 2024

Extensive literature shows multiple genetic loci's involvement in regulating pioglitazone's action in diabetic patients; most of the available literature lacks replication, and it is difficult to separate true positives from false-positive loci. To overcome the inconsistency in pharmacogenetics and pharmacogenomics data, we performed evidence-based semi-automated prioritization and scoring of candidate genes of pioglitazone in diabetic patients. We developed a Python script and searched with MeSH terms of "Pioglitazone (PIO)" and synonyms," and (i) built a complete library of published data (22,532 publications), (ii) extracted sentences containing pioglitazone-gene pair by using Python 3.6, (iii) annotated each sentence for its relevance, (iv) developed evidence scoring algorithm based on pharmacogenomics relatedness, frequency, and consistency. From the literature, we have identified that the gene encoding peroxisome proliferator-activated receptor gamma showed the strongest evidence of mediating the pioglitazone response. Additionally, polymorphisms in genes affecting the pharmacokinetics were from the Cytochrome enzyme family, i.e., Cyp2C8, Cyp3A4, and Cyp2C9, and pharmacodynamics were protein tyrosine phosphokinase (Ptprd), Lipoprotein (Lpl), Adiponectin receptor 2 (Adipora2), and PPARG coactivator 1 alpha (Ppargc1). Furthermore, drug-induced adverse drug reactions were associated with polymorphisms in the Solute carrier family 12 member 1 (Scl12a1) and Aquaporin 2 (Aqp2) genes. We have prioritized candidate gene variants and their response to pioglitazone in diabetic patients. Our results showed PPAR-α receptors/ PPARG as one of the most robust evidence of therapeutic response to pioglitazone and highlighted other variants in different pathways. However, we further warrant validation of our results in a large drug response GWAS dataset.
Impact of CYP3A5 Genotype on De-novo LCP Tacrolimus Dosing in Kidney Transplantation
Authors: Staff Editorial 
Published: May 2024

The CYP3A5 gene encodes an enzyme called cytochrome P450 3A5, which is involved in the metabolism of many drugs, including tacrolimus. Tacrolimus is an immunosuppressive medication commonly used in kidney transplantation to prevent organ rejection. The CYP3A5 genotype can influence the metabolism and clearance of tacrolimus, leading to variations in the drug levels and response. LCP tac (an extended-release form of tacrolimus) has a recommended starting dose of 0.14 mg/kg/day in kidney transplants. Rao et al assessed the influence of CYP3A5 genotypes on perioperative LCP tac dosing and monitoring in adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured, and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele). They concluded that CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers. Pharmacogenet Genomics. 2023 Apr 1;33(3):59-65. doi: 10.1097/FPC.0000000000000494.
Predictors of Voriconazole Concentration in Hematopoietic Stem Cell Transplant
Authors: Staff Editorial 
Published: May 2024

The variability in individual response to voriconazole can be influenced by both genetic factors (pharmacogenetics) and clinical factors. Understanding the pharmacogenetic and clinical predictors of voriconazole response is important for optimizing its use and minimizing adverse effects. Patel and colleagues investigated the association of genetic polymorphisms in ABCB1, ABCG2, CYP2C9, CYP3A4, CYP3A5, and the CYP2C genes with voriconazole trough concentrations in patients receiving CYP2C19-guided dosing. They performed a retrospective study in allogeneic hematopoietic cell transplant patients receiving CYP2C19-guided voriconazole dosing. They found that 36% of 185 patients were subtherapeutic. They also found that CYP2C19, age, and letermovir use were associated with voriconazole concentrations. Variations in the ABCG2 gene were associated with voriconazole concentrations in patients receiving 200 mg dose. Genetic polymorphisms in CYP2C19 and letermovir use were associated with subtherapeutic status. They concluded that CYP2C19 phenotype and letermovir use were significantly associated with subtherapeutic voriconazole concentrations and may be used to improve voriconazole precision dosing. Pharmacogenomics J. 2023 Nov;23(6):201-209. doi: 10.1038/s41397-023-00320-z.
Peripheral Neuropathy Patients and the Effectiveness of Crocin of Saffron (Crocus Sativus L.)
Authors: Editorial Staff  
Published: May 2024

Cancer patients treated with chemotherapeutic drugs often suffer from Chemotherapy-induced peripheral neuropathy (CIPN). In animal models, peripheral neuropathy has been diminished by the use of Saffron. A previous clinical trial has demonstrated that Saffron has the ability to relieve pain in patients suffering from fibromyalgia. Bozorgi and colleagues have for the very first time, studied the potential analgesic properties of an important constituent of Saffron- Crocin. Between December 2018 and March 2020, a total of 177 eligible patients suffering from mild to moderate CIPN for at least a month were recruited for the trial. The patients were categorized into two main groups: Placebo tablet and Crocin 15 mg tablet twice a day for a duration of 8 weeks. A crossover study design with a washout period of 2 weeks was adopted. Their study revealed that a significant decline in neuropathic, sensory, and motor pain was observed in the Crocin group vs the placebo group. Only mild toxicity and no significant difference in adverse effects were seen between the two groups. The authors argue that Crocin does have the ability to substantially reduced CIPN in cancer patients undergoing chemotherapy. Nonetheless, the authors also suggest further investigations, especially compared to Lamotrigine, gabapentin, and antidepressants. J Ethnopharmacol. 2021 Dec 5;281:114511.
SARS-Cov-2 Inhibition by Cannabidiol.
Authors: Editorial Staff  
Published: May 2024

Besides lungs, intestines possess a high density of the Angiotensin-Converting Enzyme (ACE-2) receptors and therefore, serve as a favorable site for SAR-CoV2 replication. In light of its anti-inflammatory and immunomodulatory potential exhibited in the lungs, Cannabidiol (CBD) has been suggested as a potential agent for managing Covid-19 infections. In an in vitro study, using Caco-2 cells, Corpetti and colleagues investigated the efficacy of CBD against hyperinflammatory responses and epithelial cell damage induced by the SARS-CoV2 spike protein. Their results revealed a PPAR-γ-dependent decrease in toxicity. Toll-like receptor 4 (TLR-4), ACE-2, inflammasome complex (NLRP3), and Caspase-1, family members of Ras homologues A-GTPase (RhoA-GTPase) were markedly decreased by the use of CBD. Enzyme-linked immunosorbent assay (ELISA) showed parallel inhibition of tumor necrosis factor-alpha (TNF-α), IL-18, interleukin 1 beta (IL-1β), and IL-6. An enhanced tight-junction protein expression along with restoration of transepithelial electrical resistance (TEER) was seen with CBD treatment. Henceforth, CBD has shown a strong in vitro inhibition of enterotoxicity induced by spike protein. Phytother Res. 2021 Dec;35(12):6893-6903.
Natural Inhibition of β-secretase in Alzheimer’s Disease by Medicinal Plants
Authors: Altaf Aisha , Akhlaq Muhammad , Uddin Jala`l , Khan Ajmal , Al-Harrasi Ahmed , Ullah Farman , Ali Fawad 
Published: May 2024

Alzheimer’s disease (AD) is the most common type of dementia, an irreversible neurodegenerative disease that worsens over time. It frequently affects the elderly population and, therefore, its prevalence is soaring in countries with a high proportion of the aging population. The incidence of AD is likely to increase further with increasing life expectancy throughout the world. There is still no sight of therapies that could stop or slow the progression of AD despite the significant expansion in our understanding of the disease at molecular, cellular, and system levels in the last 50 years. The only medications approved by the Food and Drug Administration (FDA), for the treatment of AD are acetylcholinesterase inhibitors (donepezil, galantamine, tacrine, and rivastigmine) and glutamate receptor antagonist (memantine). Apart from acetylcholinesterase inhibition, another important therapeutic target for treating AD is the inhibition of β‐site APP cleaving enzyme‐1 (BACE1), which is involved in the proteolysis of the amyloid precursor protein (APP) leading to the formation of neurotoxic amyloid β (Aβ) protein. Extensive research following this approach has led to the rationally designed synthetic, and potent BACE1 inhibitors, several of which are in clinical trials. However, the high failure rate of the BACE1 inhibitors in clinical trials necessitates finding a different source of BACE1 inhibitors. In this review, we discuss the most promising phytocompounds and plant extracts showing potent BACE1 inhibitory activity. Future research directions are suggested and recommendations are made to expand the use of medicinal plants and their formulations to prevent, mitigate and treat AD.
Rhein Inhibits PI3K/Akt/mTOR Signaling Pathway to Show Efficacy in an Ulcerative Colitis Mice Model
Authors: Editorial Staff  
Published: May 2024

Dong and his associates investigated the potential therapeutic effect of Rhein on ulcerative colitis (UC) and its mechanism in mouse models of human disease. Their results showed a decrease in the levels of TNF-α, IL-6, IL-1β, and other cytokines responsible for promoting inflammation. Moreover, both in-vivo and in-vitro mitigation of UC-associated symptoms such as colon shortening, weight loss, diarrhea, and hematochezia stimulated by dextran sodium sulfate was seen. Through western blotting, decreasing phosphorylated protein levels of PI3K, Akt, mTOR, and p70S6K1 by Rhein was evident which indicates inhibition of the PI3K/Akt/mTOR signaling pathway. Rhein administration also partially reversed the gut dysbacteriosis of mice induced by dextran sulfate sodium. A decrease in pathogenic bacteria (e.g., Enterobacteriaceae and Turicibacter) as revealed by 16sRNA gene sequencing was also observed. The authors conclude that Rhein possesses anti-UC activity as exhibited by alleviating the signs and symptoms of UC and diminishing gastrointestinal inflammation by blocking the PI3K/Akt/mTOR signaling pathway and modulating stomach microbiota. Phytother Res. 2022 May;36(5):2081-2094.
A Traditional Chinese Remedy for Hepatocellular Carcinoma Functions by Suppressing Exosomal miR-23a-3p/Smad Signaling
Authors: Editorial Staff  
Published: May 2024

A decoction of Jianpi Huayu (JHP) has been used traditionally in orthodox Chinese medicine to treat tumors such as hepatocellular carcinoma (HCC), however, the mechanism is still a mystery. Intercellular communication in the cancer cell microenvironment points toward a strong role of exosomes, but their contribution to HCC is still not well understood. Xie and colleagues investigated the anti-neoplastic effects of JHD and the possible function of exosomal signaling. Nude mice models with subcutaneous cancer were used to gauge the effects of JHD. Migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT) of cultured HCC cells were mitigated by JHD. From the EMT-induced HCC cells, exosomes increased the invasion, migration, and EMT of other cultured HCC cells, whereas post-treatment of JHD, exosomes from EMT-induced HCC cells had little effect. Exosomal miR-23a-3p which is significantly upregulated in cancer cells as compared to normal cells was reduced in JHD-treated cultured HCC cells. Post hepatectomy, patients with high miR-23a-3p levels had low survival rates. Smad signaling protein expression as well HCC cell proliferation was upregulated by miR-23a-3p. More critically, miR-23a-3p overexpression countered the EMT and Smad signaling inhibition brought about by JHD treatment. In vivo examinations revealed that treatment with JHD additionally diminished the development of HCC-derived tumors in naked mice, and decreased the levels of miR-23a-3p in serum exosomes and the degree of EMT in cancer cells. The authors conclude that the anticancer properties of JHD partially if not completely are due to the downregulation of exosome-mediated intercellular miR-23a-3p transfer and subsequent blockade of Smad signaling. Disrupting this exosomal miR-23a-3p/Smad signaling pathway may be an effective treatment. J Ethnopharmacol. 2022 Aug 10;294:115360.
Wound Healing by Italian and Algerian Resins
Authors: Editorial Staff  
Published: May 2024

One of the most common traditional medicine remedies used for wound healing is the oleoresin preparation of Pistacia vera. However, no scientific rationale has been provided for the wound healing properties of the plant and its resins. Boudjelal and associates using a circular wound healing model assessed the ability of the plant collected from Algeria and Italy for in-vivo wound healing. Their results exhibited a high terpenoid content in the plant and significant healing effects. From day 8 to day 16 significant wound contraction was seen upon application of Algerian and Italian oleoresin ointment preparation. The results were comparable to the standard drug used, Cicatryl. Histological tissue results corroborated the in vivo results. The lack of toxicity was confirmed by applying the ointments to the skins of rabbits. The authors argue that their investigation supports the traditional practice of using Pistacia vera as an effective remedy for healing wounds and injuries. Fitoterapia. 2022 Jun;159:105197.
A Chinese Decoction Arrests Lung Cancer
Authors: Editorial Staff  
Published: May 2024

A leading cause of cancer-associated deaths worldwide is lung cancer. During cancer growth, intermittent hypoxia (IH) is most commonly caused due to abnormal microcirculation and serves to promote the division and migration of cancer cells. Previous studies have established that exposure to IH is linked to Qi and Yin Syndrome (DQYS), where individuals suffering from advanced lung cancer have demonstrated deficiencies. It has been reported that an herbal remedy referred to as the Shashen-Maidong Decoction (SMD) can treat lung cancer by nourishing the body's "zheng qi" and resisting "xie qi". Currently, the same preparation is being used to address DQYS in clinical practice. Still, regarding IH, the benefits of the SMD are yet to be fully explained. In an attempt to address this gap, the underlying mechanism of action and subsequent effects of SMD were investigated by Zheng and associates in non-small cell lung cancer (NSCLC). Lewis Lung Cancer (LLC) cells were administered into the right axilla of C57 mice and afterward subjected to conditions of IH for 21 days (21%-5% O 2, 5 min/cycle, eight h/day). Thirty minutes before IH exposure, the mice were given SMD orally in three concentrations: (2.6, 5.2, or 10.4 g/kg/day). Hematoxylin-Eosin (HE) staining and Immunohistochemistry (IHC) techniques were used to gauge the proliferation and migration of tumor cells. Oxidative stress was measured through dihydroethidium (DHE) staining along with malondialdehyde (MDA) and superoxide dismutase (SOD) quantitation. Inflammatory markers IL-6, IL-1β, and TNF-α levels via IHC staining were determined, and western blotting was employed to detect the involvement of the IL-6/JAK2/STAT3 signaling pathway. LLC-injected mice given SMD exhibited markedly lowered tumor growth and hepatic metastasis. Furthermore, decreased VEGF, Ki67, MMP-2, and CD31 were seen. Moreover, elevated expression in tumor tissue of E-cadherin was observed. Reduction in NOX-2 expression, MDA levels, enhanced expression of SOD-2, and increased levels of SOD are evidence of the anti-oxidant potential of SMD. Diminished IL-6, IL-1β, and TNF-α levels, decreased IL-6 expression, and reduced JAK2 and STAT3 phosphorylation were also seen with SMD.Additionally, SMD treatment improved DQYS and liver and kidney function in LLC-bearing mice under IH conditions. Therefore, their investigation reasonably demonstrates that SMD treatment bears tumor-inhibiting potential under IH conditions in LLC-bearing mice. Inactivation of the IL-6/JAK2/STAT3 signaling pathway under IH conditions may be the underlying reason for the anti-oxidant and anti-inflammatory and the resultant anti-neoplastic effects of SMD. J Ethnopharmacol (2022) DOI: 10.1016/j.jep.2022.115654.
Inula Japonica Alleviates Inflammation and Oxidative Stress in LPS-Induced Acute Lung Injury
Authors: Editorial Staff  
Published: May 2024

Presenting as atelectasis and pulmonary edema, acute lung injury (ALI) is a life-threatening condition. Inula japonica Thunb is a Chinese herbal medicine traditionally used for treating lung diseases. Nonetheless, the underlying mechanisms of the terpenoids present in the plant remain to be elucidated. In mouse models with lipopolysaccharide (LPS) induced ALI, the protective effects of total terpenoids of Inula japonica (TTIJ) were studied. ALI was developed in the mice by injecting LPS into the trachea. The underlying mechanism of TTIJ was determined using bioinformatic and RNA-seq technology. For oxidative stress and inflammation, the effects of TTIJ were verified using real-time qPCR and western blotting.
In the lungs, LPS-caused histopathological changes were markedly inhibited by TTIJ. Two major pathways were identified, nuclear factor-erythroid 2-related factor 2 (Nrf2) and Toll-like receptor 4 (TLR4), primarily responsible for the TTIJ protective effects. A drastically reduced inflammation and oxidative stress in LPS-induced ALI was seen through the modulation of anti-oxidative cytokines, glutathione (GSH) and superoxide dismutase (SOD), as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), upon pretreatment with TTIJ. The inactivation of the MAPK/NF-κB signaling pathway reduced the phosphorylation of p65, p38, JNK, and ERK. TTIJ successfully suppressed cyclooxygenase-2 (COX-2) expression. As confirmed by the luciferase assay, several integral components of Nrf2 signaling pathways were elevated via Nrf2 receptor activation. These authors showed that TTIJ could serve as a potential therapeutic agent for ALI due to the anti-oxidant and anti-inflammatory properties Phytomedicine (2022) DOI: 10.1016/j.phymed.2022.154377.
Alleviation of Dexamethasone-induced Inhibition of Bone Formation by Salidroside
Authors: Staff Editorial 
Published: May 2024

Salidroside is a natural compound found in the plant Rhodiola rosea. It has been the subject of scientific research due to its potential health benefits. Xie and colleagues investigated the effect of salidroside on dexamethasone-induced inhibition of bone formation and found that it may alleviate this inhibition. The study investigated whether salidroside could counteract the inhibitory effects of dexamethasone on bone formation. The researchers focused on the TGF-β/Smad2/3 signaling pathway, which plays a crucial role in regulating bone metabolism. Salidroside increased the expression of osteopontin (OPN), runt-related transcription factor 2 (Runx2), osterix (Osx), transforming growth factor-beta (TGF-β) proteins and promoted the phosphorylation of Smad2/3 in MC3T3-E1 cells treated with dexamethasone. The results of the study demonstrated that salidroside treatment mitigated the dexamethasone-induced inhibition of osteogenic differentiation and bone formation. Salidroside was found to promote the activation of the TGF-β/Smad2/3 signaling pathway, which is involved in bone formation and remodeling processes. Phytother Res. 2023 May;37(5):1938-1950. doi: 10.1002/ptr.7711.
Curcumol Attenuates Human Uterine Leiomyoma Cell Development
Authors: Staff Editorial 
Published: May 2024

Curcumol is a major terpenoid compound derived from Curcumae Rhizoma, the rhizome of the plant Curcuma wenyujin. It has been studied for its potential therapeutic properties, including its effects on human uterine leiomyoma cell development. Yu and colleagues investigated the impact of curcumol on uterine leiomyoma cells and found that it may attenuate their development. Uterine leiomyomas, also known as uterine fibroids, are benign tumors that develop in the smooth muscle layer of the uterus. They are the most common type of uterine tumor in women of reproductive age and can cause various symptoms, including heavy menstrual bleeding, pelvic pain, and reproductive issues. The study aimed to explore the effects of curcumol on the development of human uterine leiomyoma cells. Curcumol was selected due to its potential anti-inflammatory and anti-proliferative properties. The results of the study indicated that curcumol treatment attenuated the development of human uterine leiomyoma cells. It achieved this effect by inhibiting the activation of the p38MAPK/NF-κB pathway. The p38MAPK (mitogen-activated protein kinase)/NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway is a signaling pathway involved in various cellular processes, including inflammation and cell proliferation. Dysregulation of this pathway has been implicated in the development and progression of various diseases, including uterine leiomyoma. Curcumol was found to suppress the phosphorylation (activation) of p38MAPK and subsequently inhibit the nuclear translocation of NF-κB. These actions resulted in decreased production of pro-inflammatory cytokines and reduced cell proliferation in uterine leiomyoma cells. It's important to note that while these findings suggest a potential therapeutic effect of curcumol on uterine leiomyoma cells, further research, including in vivo studies and clinical trials, is needed to validate these findings and determine the optimal use of curcumol in the management of uterine leiomylomas. J Ethnopharmacol. 2023 Jun 28;310:116311. doi: 10.1016/j.jep.2023.116311.
Anti-inflammatory Actions of Praxelis Clematidea
Authors: Staff Editorial 
Published: May 2024

Praxelis clematidea is a plant species that belongs to the Asteraceae family. It is native to South America and has been traditionally used in folk medicine for its medicinal properties. Researchers have investigated the chemical constituents of Praxelis clematidea and identified several anti-inflammatory phenolics and phenylpropanoids. Here is some information about these compounds: The anti-inflammatory properties of Praxelis clematidea phenolics and phenylpropanoids make them of interest for potential therapeutic applications. Studies have identified various phenolics and phenylpropanoids in Praxelis clematidea, including flavonoids, caffeic acid derivatives, coumarins, and lignans. Some of the specific compounds reported include clematidin, clematomandshurin, clematoside-I, clematoside-II, and praxelin. Liang and his colleagues have demonstrated the anti-inflammatory activity of these compounds. They have been shown to inhibit the production of pro-inflammatory molecules, such as nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). They can inhibit the activation of transcription factors like nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), which are key regulators of inflammatory responses. The authors concluded that given their anti-inflammatory properties, the phenolics and phenylpropanoids from Praxelis clematidea have the potential for use in the development of natural anti-inflammatory agents or as leads for drug discovery targeting inflammation-related conditions. Fitoterapia. 2023 Jun;167:105476. doi: 10.1016/j.fitote.2023.105476.