bluuebunny/crossref_metadata_2025 huggingface dataset:
UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol’s Metabolic Target in Endometriosis
Authors: Liu Jing , Yang Dongxia , Piao Chengyu , Wang Xu , Sun Xiaolan , Li Yongyan , Zhang Shuxiang , Wu Xiuhong
Published: January 2023

Endometriosis is a common gynecological illness in women of reproductive age that significantly decreases life quality and fertility. Paeonol has been shown to play an important part in endometriosis treatments. Understanding the mechanism is critical for treating endometriosis. In this study, autologous transplantation combined with a 28 day ice water bath was used to create a rat model of endometriosis with cold clotting and blood stagnation. The levels of estradiol and progesterone in plasma were detected by ELISA, and the pathological changes of ectopic endometrial tissue were examined by H&E staining, which proved the efficacy of paeonol. For metabolomic analysis of plasma samples, UPLC-Q/TOF-MS was combined with multivariate statistical analysis to identify the influence of paeonol on small molecule metabolites relevant to endometriosis. Finally, the key targets were screened using a combination of network pharmacology and molecular docking approaches. The results showed that the pathological indexes of rats were improved and returned to normal levels after treatment with paeonol, which was the basis for confirming the efficacy of paeonol. Metabolomics results identified 13 potential biomarkers, and paeonol callbacks 7 of them, involving six metabolic pathways. Finally, four key genes were found for paeonol therapy of endometriosis, and the results of molecular docking revealed a significant interaction between paeonol and the four key genes. This study was successful in establishing a rat model of endometriosis with cold coagulation and blood stagnation. GCH1, RPL8, PKLR, and MAOA were the key targets of paeonol in the treatment of endometriosis. It is also demonstrated that metabolomic techniques give the potential and environment for comprehensively understanding drug onset processes.
Nanotechnology: A Revolution in Modern Industry
Authors: Malik Shiza , Muhammad Khalid , Waheed Yasir
Published: January 2023

Nanotechnology, contrary to its name, has massively revolutionized industries around the world. This paper predominantly deals with data regarding the applications of nanotechnology in the modernization of several industries. A comprehensive research strategy is adopted to incorporate the latest data driven from major science platforms. Resultantly, a broad-spectrum overview is presented which comprises the diverse applications of nanotechnology in modern industries. This study reveals that nanotechnology is not limited to research labs or small-scale manufacturing units of nanomedicine, but instead has taken a major share in different industries. Companies around the world are now trying to make their innovations more efficient in terms of structuring, working, and designing outlook and productivity by taking advantage of nanotechnology. From small-scale manufacturing and processing units such as those in agriculture, food, and medicine industries to larger-scale production units such as those operating in industries of automobiles, civil engineering, and environmental management, nanotechnology has manifested the modernization of almost every industrial domain on a global scale. With pronounced cooperation among researchers, industrialists, scientists, technologists, environmentalists, and educationists, the more sustainable development of nano-based industries can be predicted in the future.
Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity
Authors: Tang Songyuan , Ren Junling , Kong Ling , Yan Guangli , Liu Chang , Han Ying , Sun Hui , Wang Xi-Jun
Published: January 2023

Ephedrae Herba (Ephedra), known as “MaHuang” in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.
Anti-Struvite, Antimicrobial, and Anti-Inflammatory Activities of Aqueous and Ethanolic Extracts of Saussurea costus (Falc) Lipsch Asteraceae
Authors: Mammate Naima , El oumari Fatima Ezzahra , Imtara Hamada , Belchkar Salim , Benjelloun Touimi Ghita , Al-Zharani Mohammed , A. Rudayni Hassan , Ahmed Qurtam Ashraf , S. Aleissa Mohammed , A. Nasr Fahd , M. Noman Omar , Sqalli Houssaini Tarik
Published: January 2023

Saussurea costus (Falc) Lipsch is a traditional herb used to treat kidney stone problems because it contains several molecules used to treat this health problem, such as quercitrin. Infectious stones are the most painful of all urinary tract disorders, with ammonium phosphate (struvite) and carbapatite stones being the most common, caused by a bacterial infection with urease activity. These stones are treated with antibiotics, but antibiotic resistance is on the rise. The current study investigated the anti-urolithic activities of S. costus aqueous and ethanolic extracts of against struvite crystals synthesized using microscopic crystallization and turbidimetric methods, respectively. The utilized methods indicated that the ethanolic extract of this plant has a significant inhibitory effect on struvite crystallization, with a percentage inhibition of (87.45 ± 1.107) (p < 0.001) for a concentration of 1 mg mL−1 and a decrease in the number of struvite crystals, reaching values less than 100/mm3. For the number of struvite crystals inhibited by cystone, we found a value of 400/mm3 and with the aqueous extract we found 700/mm3. The antibacterial activity of the plant extracts studied was examined against several urease-producing bacteria, and this activity was evaluated by qualitative and quantitative evaluation methods; the highest minimum inhibitory concentration was seen in the ethanolic extract, with an MIC of 50 mg mL−1 for Staphylococcus aureus followed by an MIC of 200 mg mL−1 for Klebsiella pneumoniae. It showed a minimal bactericidal concentration (MBC) against S. aureus and K. pneumoniae (>50 mg mL−1 and >200 mg mL−1, respectively). Furthermore, to determine the extract’s anti-inflammatory activity, in vivo anti-inflammatory activity was investigated in rats. The results show that at a dose of 400 mg kg−1, the ethanolic extract has a maximum edema inhibition of 66%.
Environmental Impact Assessment for Animal Waste, Organic and Synthetic Fertilizers
Authors: Litskas Vassilis D.
Published: January 2023

The use of fertilizers is of the utmost importance for food security on a global scale. However, fertilizer production and overuse may yield environmental issues. In this research, Life Cycle Assessment (LCA) was used to estimate eighteen environmental impact categories for six different fertilizer products: three synthetic (ammonium nitrate; calcium ammonium nitrate; and urea ammonium nitrate) and three organic (cattle manure; compost; and a mixture of compost and synthetic fertilizer). The processes for fertilizer production were obtained from the Agribalyse database. The system boundaries were from cradle to factory gate (or farm gate in the case of animal waste), and the impact indicators were calculated per kg of nitrogen (N). The data showed that the organo-mineral fertilizer (a mix of compost and synthetic fertilizer) had the highest environmental impact according to the results for most of the impact categories. The median values for this product regarding water consumption, fossil resource use and global warming potential were 322.5 L, 3.82 kg oil equivalent and 13.70 kg CO2 equivalent, respectively, per kg of N. The respective values for cattle manure, for which the lowest environmental impact was observed, were 0.23 L of water, 0.002 kg oil-eq and 3.29 kg of CO2-eq, respectively, per kg of N. Further research should focus on the determination of the impact from other stages of the life cycle (e.g., transportation and application to the field) which were not included in this work. This research could support the selection of N fertilizer in sustainable food production.
Postbiotics in Human Health: A Narrative Review
Authors: Ma Linxi , Tu Huaijun , Chen Tingtao
Published: January 2023

In the 21st century, compressive health and functional foods are advocated by increasingly more people in order to eliminate sub-health conditions. Probiotics and postbiotics have gradually become the focus of scientific and nutrition communities. With the maturity and wide application of probiotics, the safety concerns and other disadvantages are non-negligible as we review here. As new-era products, postbiotics continue to have considerable potential as well as plentiful drawbacks to optimize. “Postbiotic” has been defined as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”. Here, the evolution of the concept “postbiotics” is reviewed. The underlying mechanisms of postbiotic action are discussed. Current insight suggests that postbiotics exert efficacy through protective modulation, fortifying the epithelial barrier and modulation of immune responses. Finally, we provide an overview of the comparative advantages and the current application in the food industry at pharmaceutical and biomedical levels.
Evaluation of Nutritional Interventions in the Care Plan for Cancer Patients: The NOA Project
Authors: García-Luna Pedro Pablo , Rabat Restrepo Juana M. , Muñoz-Ayllón Marta , de la Calle Gil Milagros , Remón Pablo , Sánchez-Torralvo Francisco José , Pachón Jerónimo , García-González Juan J. , García-Manrique Teresa , Salvador-Bofill Javier , Vicente David , Olveira Gabriel
Published: January 2023

The NOA (Oncological Nutrition in Andalusia) project analyses the degree of integration and areas of improvement in implementing nutritional support in the care plans of cancer patients in Andalusia. The aim was to analyse nutritional interventions for better care of cancer patients and for the improvement of the management of malnutrition in cancer. A prospective evaluation of the implementation of two areas of improvement in nutrition was conducted in three hospitals. Data were collected from each hospital over a six-month period using an online platform. A standardised care plan was designed for hospitals in Andalusia, in which proposed improvements were devised and prioritised, selecting nutritional screening in oncology services and the participation of the Nutrition Support Team (NST) on the tumour boards, as well as the assessment of the patients presented at these sessions. Our results indicated an increase in the number of medical records with nutritional evaluation results six months later, regardless of the type of tumour or hospitalisation; and there was greater participation of the NST on the tumour boards, mainly for head and neck and oesophagogastric cases. Solutions for improvement have been pinpointed and implemented that have positively impacted the nutritional care plan in the course of oncological disease.
Emotional Eating and Binge Eating Disorders and Night Eating Syndrome in Polycystic Ovary Syndrome—A Vicious Circle of Disease: A Systematic Review
Authors: Burnatowska Ewelina , Wikarek Agnieszka , Oboza Paulina , Ogarek Natalia , Glinianowicz Mateusz , Kocelak Piotr , Olszanecka-Glinianowicz Magdalena
Published: January 2023

Obesity is an established risk factor for the development of polycystic ovary syndrome (PCOS), especially phenotype A. PCOS is an important cause of fertility disorders in a large group of women of reproductive age. For many years, effective methods of treating hormonal disorders associated with PCOS have been sought in order to restore ovulation with regular menstrual cycles. Numerous studies support obesity treatment as an effective therapeutic method for many women. A seemingly simple method of treatment may prove to be particularly difficult in this group of women. The reason for this may be the lack of recognition the primary cause of obesity development or the occurrence of a vicious circle of disease. Primary causes of developing obesity may be emotional eating (EE) and eating disorders (EDs), such as binge eating disorder (BED) and its extreme form, addictive eating, as well as night eating syndrome (NES). All of these are caused by impaired function of the reward system. Consequently, these disorders can develop or be exacerbated in women with obesity and PCOS as a result of depression and anxiety related to hirsutism and fertility disturbances. Therefore, for the effective treatment of obesity, it is very important to recognize and treat EE, BED, and NES, including the appropriate selection of pharmacotherapy and psychotherapy. Therefore, the aim of our manuscript is to analyze the available data on the relationships between EE, BED, NES, obesity, and PCOS and their impact on the treatment of obesity in women with PCOS.
Fermentation of Abelmoschus manihot Extract with Halophilic Bacillus licheniformis CP6 Results in Enhanced Anti-Inflammatory Activities
Authors: Park Mi Hwa , Yeom Yu Jeong , Ganbat Dariimaa , Kim Min Kyeong , Kim Seong-Bo , Lee Yong-Jik , Lee Sang-Jae
Published: January 2023

Microbial fermentation provides a valorization strategy, through biotransformation, to convert plant-derived raw materials into health-promoting agents. In this study, we have investigated the antioxidative activity of Abelmoschus manihot fermented with various Bacillaceae strains from specific environments and demonstrated the anti-inflammatory effects of Bacillus licheniformis CP6 fermented A. manihot extract (FAME) in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. Of 1500 bacteria isolated from various specific environments, 47 extracellular protease- and amylase-producing strains with qualified presumption safety status, belonging to the family Bacillaceae, were selected for A. manihot fermentation. Among them, strain CP6, a halophilic bacterium isolated from Tongyeong seawater in Korea and identified as B. licheniformis, showed the highest antioxidant activity. In particular, FAME exerted anti-inflammatory effects on LPS-stimulated Raw264.7 macrophages. Consequently, FAME had a potent inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages, without cytotoxicity. Moreover, FAME downregulated LPS-induced pro-inflammatory mediator and enzyme levels in LPS-induced Raw264.7 cells, including IL-1β, IL-6, TNF-α, iNOS, and COX-2, compared to levels when cells were incubated in A. manihot extract (IAME). Further detailed characterization indicated that FAME suppresses inflammation by blocking NF-κB via IKK phosphorylation inhibition and IκB-α degradation and by downregulating NO production, and inflammatory mediators also decreased NF-κB translocation. Furthermore, FAME inhibited LPS-stimulated activation of MAPKs, including ERK1/2, JNK, and p38, compared to that with either IAME. Therefore, we suggest that FAME could be used for inflammation-related disorders.
Hospital Services to Improve Nutritional Intake and Reduce Food Waste: A Systematic Review
Authors: Rinninella Emanuele , Raoul Pauline , Maccauro Valeria , Cintoni Marco , Cambieri Andrea , Fiore Alberto , Zega Maurizio , Gasbarrini Antonio , Mele Maria Cristina
Published: January 2023

Background and Aims: Patients’ nutritional intake is a crucial issue in modern hospitals, where the high prevalence of disease-related malnutrition may worsen clinical outcomes. On the other hand, food waste raises concerns in terms of sustainability and environmental burden. We conducted a systematic review to ascertain which hospital services could overcome both issues. Methods: A systematic literature search following PRISMA guidelines was conducted across MEDLINE, Web of Science, and Scopus for randomised controlled trials (RCTs) and observational studies comparing the effect of hospital strategies on energy intake, protein intake, and plate/food waste. The quality of included studies was assessed using the Newcastle-Ottawa Scale for cohort studies and the Cochrane Risk of Bias tool from the Cochrane Handbook for Systematic Reviews of Interventions for RCTs. Results: Nineteen studies were included, assessing as many hospital strategies such as food service systems—including catering and room service—(n = 9), protected mealtimes and volunteer feeding assistance (n = 4), food presentation strategies (n = 3), nutritional counseling and education (n = 2), plant-based proteins meal (n = 1). Given the heterogeneity of the included studies, the results were narratively analysed. Conclusions: Although the results should be confirmed by prospective and large sample-size studies, the personalisation of the meal and efficient room service may improve nutritional intake while decreasing food waste. Clinical nutritionist staff—especially dietitians—may increase food intake reducing food waste through active monitoring of the patients’ nutritional needs.
Clinical Outcome of Coronavirus Disease 2019 in Patients with Primary Antibody Deficiencies
Authors: Milota Tomas , Smetanova Jitka , Bartunkova Jirina
Published: January 2023

In 2019, the novel coronavirus, SARS-CoV-2, caused a worldwide pandemic, affecting more than 630 million individuals and causing 6.5 million deaths. In the general population, poorer outcomes have been associated with older age, chronic lung and cardiovascular diseases, and lymphopenia, highlighting the important role of cellular immunity in the immune response against SARS-CoV-2. Moreover, SARS-CoV-2 variants may have a significant impact on disease severity. There is a significant overlap with complications commonly found in inborn errors of immunity (IEI), such as primary antibody deficiencies. The results of various studies have provided ambiguous findings. Several studies identified risk factors in the general population with a minor impact on SARS-CoV-2 infection. However, other studies have found a significant contribution of underlying immunodeficiency and immune-system dysregulation to the disease course. This ambiguity probably reflects the demographic differences and viral evolution. Impaired antibody production was associated with prolonged viral shedding, suggesting a critical role of humoral immunity in controlling SARS-CoV-2 infection. This may explain the poorer outcomes in primary antibody deficiencies compared to other IEIs. Understanding coronavirus disease 2019 (COVID-19) pathogenesis and identifying risk factors may help us identify patients at high risk of severe COVID-19 for whom preventive measures should be introduced.
Tramadol and Tapentadol Induce Conditioned Place Preference with a Differential Impact on Rewarding Memory and Incubation of Craving
Authors: Barbosa Joana , Leal Sandra , Pereira Frederico C. , Dinis-Oliveira Ricardo Jorge , Faria Juliana
Published: January 2023

Tramadol and tapentadol, synthetic opioids commonly prescribed for moderate-to-severe pain, have a unique pharmacology that optimizes their analgesia and safety. However, they are not devoid of risks, presenting addictive, abuse, and dependence potential. While tramadol-reinforcing properties have been documented by various studies with human and animal models, including conditioned place preference (CPP) assays, no similar studies have been performed with tapentadol. In the present study, we performed CPP assays by intraperitoneally administering Wistar rats with a tramadol/tapentadol therapeutic dose. Animal permanence and the number of entries in the CPP compartments were recorded in the preconditioning phase and then 1 (T1), 7 (T7), and 14 (T14) days after conditioning. Both opioids induced a change in place preference (T1), suggesting that they have short-term reinforcing properties. However, only tramadol was associated with place preference retention (T7 and T14), with an increase in the number of entries in the opioid-paired compartment (T1 and T7), showing that it causes rewarding memory and incubation of craving. The results indicate that at therapeutic doses: (1) both drugs cause short-term rewarding effects and (2) as opposed to tramadol, tapentadol does not cause CPP retention, despite its higher central nervous system activity and stricter scheduling.
Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway
Authors: Xu Baiyang , Yao Mengxue , Liu Zilu , Zhang Shanshan , Wang Bin , Han Yanquan , Gao Jiarong , Wu Deling , Wang Xiaoli
Published: January 2023

The Stephania tetrandra–Astragalus membranaceus herbal pair (FH) is a classic herbal pair widely used in the treatment of nephrotic syndrome (NS). The effects of Stephania tetrandra (FJ) and Astragalus membranaceus (HQ) on NS have been reported, but the mechanism of their combination on the improvement of NS are still unclear. The NS model was established by injecting adriamycin into the tail vein. FH intervention reduced the levels of serum triglyceride, total cholesterol, interleukin-6 (IL-6), blood urea nitrogen (BUN), urinary protein, and the gene expression levels of aquaporin 2 (AQP2) and arginine vasopressin (AVP) in NS rats. In addition, FH improved kidney injury in NS rats by inhibiting the expression of interleukin 13 (IL-13), phospho-signal transducers, and activators of transcription 6 (p-STAT6), Bax, cleaved-caspase3, while promoting the expression of Bcl-2. By comprehensive comparison of multiple indexes, the effects of FH on lipid metabolism, glomerular filtration rate, and inflammation were superior to that of FJ and HQ. Metabonomic studies showed that, compared with FJ and HQ, FH intervention significantly regulated tricarboxylic acid (TCA) cycle, cysteine and methionine metabolism, and alanine, aspartic acid and glutamic acid metabolism. Pearson correlation analysis showed that succinic acid and L-aspartic acid were negatively correlated with urinary protein, cystatin C (Cys C) and BUN (p < 0.05). In summary, FH could reduce renal injury and improve NS through inhibiting the IL-13/STAT6 signal pathway, regulating endogenous metabolic pathways, such as TCA cycle, and inhibiting the expression of AQP2 and AVP genes. This study provides a comprehensive strategy to reveal the mechanism of FH on the treatment of NS, and also provides a reasonable way to clarify the compatibility of traditional Chinese medicine.
Refractory Age-Related Macular Degeneration Due to Concurrent Central Serous Chorioretinopathy in Previously Well-Controlled Eyes
Authors: Hara Chikako , Wakabayashi Taku , Sayanagi Kaori , Nishida Kohji
Published: January 2023

Background: During the treatment of age-related macular degeneration with anti-vascular endothelial growth factor (VEGF) drugs, we often see cases with anti-VEGF-resistant refractory subretinal fluid. In this report, we present two cases of anti-VEGF-resistant refractory age-related macular degeneration (AMD) due to the concurrent development of central serous chorioretinopathy (CSCR) in eyes previously well controlled with intravitreal anti-VEGF injections. Case presentation: Two patients underwent intravitreal aflibercept for the treatment of neovascular AMD. Initially, both patients responded well to intravitreal aflibercept, resulting in the complete resolution of the subretinal fluid. However, both patients subsequently developed sudden-onset refractory subretinal fluid that did not respond to repeated intravitreal aflibercept. Fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography revealed focal leakage spots, choroidal hyperpermeability, and dilated choroidal vessels, respectively, which were distinct from the pre-existing choroidal neovascularization and suggestive of newly developed CSCR. Laser photocoagulation of the leak spots resulted in the complete resolution of the once-refractory subretinal fluid and the maintenance of vision. Conclusions: Our cases highlight that anti-VEGF-refractory subretinal fluid may occur secondary to concurrent CSCR in patients receiving regular anti-VEGF treatments for AMD. In those patients, treatment for CSCR is effective for controlling subretinal fluid that is unresolved by anti-VEGF treatment.
Ocular Delivery of Therapeutic Proteins: A Review
Authors: Shastri Divyesh H. , Silva Ana Catarina , Almeida Hugo
Published: January 2023

Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed.
Recent Advances in Intranasal Liposomes for Drug, Gene, and Vaccine Delivery
Authors: Duong Van-An , Nguyen Thi-Thao-Linh , Maeng Han-Joo
Published: January 2023

Liposomes are safe, biocompatible, and biodegradable spherical nanosized vesicles produced from cholesterol and phospholipids. Recently, liposomes have been widely administered intranasally for systemic and brain delivery. From the nasal cavity, liposome-encapsulated drugs and genes enter the systemic circulation primarily via absorption in the respiratory region, whereas they can be directly transported to the brain via the olfactory pathway. Liposomes can protect drugs and genes from enzymatic degradation, increase drug absorption across the nasal epithelium, and prolong the residence time in the nasal cavity. Intranasal liposomes are also a potential approach for vaccine delivery. Liposomes can be used as a platform to load antigens and as vaccine adjuvants to induce a robust immune response. With the recent interest in intranasal liposome formulations, this review discusses various aspects of liposomes that make them suitable for intranasal administration. We have summarized the latest advancements and applications of liposomes and evaluated their performance in the systemic and brain delivery of drugs and genes administered intranasally. We have also reviewed recent advances in intranasal liposome vaccine development and proposed perspectives on the future of intranasal liposomes.
Extemporaneous Preparation of 20 mg/mL Ganciclovir in Artificial Tears in Comparison with Sterile Water for Ophthalmic Administration: Formulation and Stability Study
Authors: Leanpolchareanchai Jiraporn , Tangteerakoon Patamaporn , Supapsophon Patcharin , Sukavatcharin Somsiri , Simaroj Pornchai , Suksiriworapong Jiraphong
Published: January 2023

Ganciclovir is available as a lyophilized powder for reconstitution and is normally used to treat ophthalmic viral infections. The use of ganciclovir in artificial tears containing hydrocolloid polymers may prove beneficial to patients during drug application, by prolonging contact time and providing a moistening effect. Therefore, this study aimed to extemporaneously prepare 20 mg/mL ganciclovir in artificial tears and compare its stability with that of a similar concentration of ganciclovir in sterile water (SWI) for ophthalmic administration. First, a compatibility study of the drug with commercial artificial tears found that it was compatible with artificial tears containing sodium hyaluronate (HYA). Subsequently, ganciclovir/0.1% HYA (HYA0.1) and ganciclovir/SWI eyedrops (EDs) in low-density polyethylene (LDPE) eyedrop bottles packed in light-shielded zipper bags were evaluated for their stability at 5 ± 3 °C and 30 ± 2 °C. The results revealed that ganciclovir/SWI ED had good physicochemical and microbiological stability when stored at 5 ± 3 °C for 12 weeks and at 30 ± 2 °C for 8 weeks. Meanwhile, ganciclovir/HYA0.1 ED was stable for 8 weeks when kept at 5 ± 3 °C and at 30 ± 2 °C, but ganciclovir in 0.3% HYA ED could be stored at 5 ± 3 °C for 8 weeks. Nevertheless, particulate matter may need to be investigated using a suitable method to ensure the absence of invisible particles in these preparations. Of these results, ganciclovir/HYA artificial tears and SWI EDs show potential for use as home medications for the treatment of ophthalmic viral infections.
Central Composite Design for Optimization of Mitomycin C-Loaded Quantum Dots/Chitosan Nanoparticles as Drug Nanocarrier Vectors
Authors: Manan Fariza Aina Abd , Yusof Nor Azah , Abdullah Jaafar , Nurdin Armania
Published: January 2023

Cancer is one of the most devastating diseases that leads to a high degree of mortality worldwide. Hence, extensive efforts have been devoted to the development of drug nanocarrier vectors as a potential new cancer treatment option. The main goal of this treatment is to deliver an anticancer medicine successfully and effectively to the patient’s cells using non-toxic nanocarriers. Here, we present a drug delivery system to emphasize the optimization of an anticancer drug-loaded formulation using Mitomycin C (MMC) encapsulated in chitosan nanocarrier conjugated with a bioimaging fluorescence probe of Mn:ZnS quantum dots (MMC@CS-Mn:ZnS). Additionally, the Response Surface Methodology (RSM), which uses a quadratic model to forecast the behaviour of the nano-drug delivery system, was used to assess the optimization of encapsulation efficiency. In this investigation, the core points of the Central Composite Design (CCD) model were used with 20 runs and 6 replications. The encapsulation efficiency (EE%) was measured using UV-Vis spectroscopy at 362 nm. The highest EE% is 55.31 ± 3.09 under the optimum parameters of incubation time (105 min), concentration of MMC (0.875 mg/mL), and concentration of nanocarriers (5.0 mg/mL). Physicochemical characterizations for the nanocarriers were accessed using a nanosizer and field-emission scanning electron microscopy (FESEM). Three independent variables for the evaluation of the encapsulation efficiency were used, in which the incubation time, concentration of MMC, concentration of nanocarriers, and correlation for each variable were studied. Furthermore, the MMC drug release efficiency was carried out in four different solution pHs of 5.5, 6.0, 6.5, 7.0, and pH 7.5, and the highest cumulative drug release of 81.44% was obtained in a pH 5.5 release medium, followed by cumulative releases of 68.55%, 50.91%, 41.57%, and 32.45% in release mediums with pH 6.0, pH 6.5, pH 7.0, and pH 7.5. Subsequently, five distinct mathematical models—pseudo-first-order, pseudo-second-order, Hixson-Crowell, Korsmeyer-Peppas, and Higuchi kinetic models—were used to fit all of the drug release data. The Korsmeyers-Peppas model was found to fit it well, highlighting its importance for the log of cumulative drug release proportional to the log of time at the equilibrium state. The correlation coefficient value (R2) was obtained as 0.9527, 0.9735, 0.9670, 0.9754, and 0.9639 for the drug release in pH 5.5, pH 6.0, pH 6.5, pH 7.0, and pH 7.5, respectively. Overall, from the analysis, the as-synthesized MMC nanocarrier (MMC@CS-Mn:ZnS) synergistically elucidates the underlying efficient delivery of MMC and leverages the drug loading efficiency, and all these factors have the potential for the simultaneous curbing of non-muscle invasive bladder cancer reoccurrence and progression when applied to the real-time disease treatment.
Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials
Authors: Andrade Stéphanie , Nunes Débora , Dabur Meghna , Ramalho Maria J. , Pereira Maria C. , Loureiro Joana A.
Published: January 2023

Neurodegenerative diseases are caused by the gradual loss of neurons’ function. These neurological illnesses remain incurable, and current medicines only alleviate the symptoms. Given the social and economic burden caused by the rising frequency of neurodegenerative diseases, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compounds’ therapeutic effects for neurodegenerative disease treatment have been investigated in numerous in vitro and in vivo studies, only few have moved to clinical trials. This article provides the first systematic review of the clinical trials evaluating natural compounds’ safety and efficacy for the treatment of the five most prevalent neurodegenerative disorders: Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease.
Lipid Nanoparticles Functionalized with Antibodies for Anticancer Drug Therapy
Authors: Marques Ana Camila , Costa Paulo C. , Velho Sérgia , Amaral Maria Helena
Published: January 2023

Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid–polymer hybrid nanoparticles—have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current “state-of-the-art” in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success.
PVA-Microbubbles as a Radioembolization Platform: Formulation and the In Vitro Proof of Concept
Authors: Da Ros Valerio , Oddo Letizia , Toumia Yosra , Guida Eugenia , Minosse Silvia , Strigari Lidia , Strolin Silvia , Paolani Giulia , Di Giuliano Francesca , Floris Roberto , Garaci Francesco , Dolci Susanna , Paradossi Gaio , Domenici Fabio
Published: January 2023

This proof-of-concept study lays the foundations for the development of a delivery strategy for radioactive lanthanides, such as Yttrium-90, against recurrent glioblastoma. Our appealing hypothesis is that by taking advantage of the combination of biocompatible polyvinyl alcohol (PVA) microbubbles (MBs) and endovascular radiopharmaceutical infusion, a minimally invasive selective radioembolization can be achieved, which can lead to personalized treatments limiting off-target toxicities for the normal brain. The results show the successful formulation strategy that turns the ultrasound contrast PVA-shelled microbubbles into a microdevice, exhibiting good loading efficiency of Yttrium cargo by complexation with a bifunctional chelator. The selective targeting of Yttrium-loaded MBs on the glioblastoma-associated tumor endothelial cells can be unlocked by the biorecognition between the overexpressed αVβ3 integrin and the ligand Cyclo(Arg-Gly-Asp-D-Phe-Lys) at the PVA microbubble surface. Hence, we show the suitability of PVA MBs as selective Y-microdevices for in situ injection via the smallest (i.e., 1.2F) neurointerventional microcatheter available on the market and the accumulation of PVA MBs on the HUVEC cell line model of integrin overexpression, thereby providing ~6 × 10−15 moles of Y90 per HUVEC cell. We further discuss the potential impact of using such versatile PVA MBs as a new therapeutic chance for treating glioblastoma multiforme recurrence.
Recent Advancements in Metallic Drug-Eluting Implants
Authors: Alshimaysawee Sadeq , Fadhel Obaid Rasha , Al-Gazally Moaed E. , Alexis Ramírez-Coronel Andrés , Bathaei Masoud Soroush
Published: January 2023

Over the past decade, metallic drug-eluting implants have gained significance in orthopedic and dental applications for controlled drug release, specifically for preventing infection associated with implants. Recent studies showed that metallic implants loaded with drugs were substituted for conventional bare metal implants to achieve sustained and controlled drug release, resulting in a desired local therapeutic concentration. A number of secondary features can be provided by the incorporated active molecules, including the promotion of osteoconduction and angiogenesis, the inhibition of bacterial invasion, and the modulation of host body reaction. This paper reviews recent trends in the development of the metallic drug-eluting implants with various drug delivery systems in the past three years. There are various types of drug-eluting implants that have been developed to meet this purpose, depending on the drug or agents that have been loaded on them. These include anti-inflammatory drugs, antibiotics agents, growth factors, and anti-resorptive drugs.
Physiological and Full-Length Transcriptome Analyses Reveal the Dwarfing Regulation in Trifoliate Orange (Poncirus trifoliata L.)
Authors: Gu Qingqing , Wei Qingjiang , Hu Yongwei , Chen Mengru , Chen Ziwen , Zheng Shuang , Ma Qiaoli , Luo Zhengrong
Published: January 2023

Dwarfing rootstocks are capable of high-density planting and are therefore urgently needed in the modern citrus cultivation system. However, little is known about the physiological relevance and molecular basis underlying citrus height. This study aimed to comprehensively analyze phytohormone, carbohydrate, and associated transcriptome changes in the stem of two weak growth rootstocks (‘TO’ and ‘FD’) relative to the vigorous ‘CC’ rootstock. The phenotypic observation revealed that the plant height, plant weight, and internode length were reduced in dwarfing rootstocks. Moreover, the contents of indole-3-acetic acid (IAA), trans-zeatin (tZ), and abscisic acid (ABA), were higher in TO and FD rootstocks, whereas the gibberellin 3 (GA3) content was higher in the CC rootstocks. The carbohydrate contents, including sucrose, fructose, glucose, starch, and lignin significantly decreased in both the TO and FD rootstocks. The full-length transcriptome analysis revealed a potential mechanism regulating dwarfing phenotype that was mainly related to the phytohormone signaling transduction, sugar and starch degradation, lignin synthesis, and cellulose and hemicellulose degradation processes. In addition, many transcription factors (TFs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) events were identified, which might act as important contributors to control the stem elongation and development in the weak growth rootstocks. These findings might deepen the understanding of the complex mechanisms of the stem development responsible for citrus dwarfing and provide a series of candidate genes for the application in breeding new rootstocks with intensive dwarfing.
Diversity of Late Blight Resistance Genes in the VIR Potato Collection
Authors: Rogozina Elena V. , Gurina Alyona A. , Chalaya Nadezhda A. , Zoteyeva Nadezhda M. , Kuznetsova Mariya A. , Beketova Mariya P. , Muratova Oksana A. , Sokolova Ekaterina A. , Drobyazina Polina E. , Khavkin Emil E.
Published: January 2023

Late blight (LB) caused by the oomycete Phytophthora infestans (Mont.) de Bary is the greatest threat to potato production worldwide. Current potato breeding for LB resistance heavily depends on the introduction of new genes for resistance to P. infestans (Rpi genes). Such genes have been discovered in highly diverse wild, primitive, and cultivated species of tuber-bearing potatoes (Solanum L. section Petota Dumort.) and introgressed into the elite potato cultivars by hybridization and transgenic complementation. Unfortunately, even the most resistant potato varieties have been overcome by LB due to the arrival of new pathogen strains and their rapid evolution. Therefore, novel sources for germplasm enhancement comprising the broad-spectrum Rpi genes are in high demand with breeders who aim to provide durable LB resistance. The Genbank of the N.I. Vavilov Institute of Plant Genetic Resources (VIR) in St. Petersburg harbors one of the world’s largest collections of potato and potato relatives. In this study, LB resistance was evaluated in a core selection representing 20 species of seven Petota series according to the Hawkes (1990) classification: Bulbocastana (Rydb.) Hawkes, Demissa Buk., Longipedicellata Buk., Maglia Bitt., Pinnatisecta (Rydb.) Hawkes, Tuberosa (Rydb.) Hawkes (wild and cultivated species), and Yungasensa Corr. LB resistance was assessed in 96 accessions representing 18 species in the laboratory test with detached leaves using a highly virulent and aggressive isolate of P. infestans. The Petota species notably differed in their LB resistance: S. bulbocastanum Dun., S. demissum Lindl., S. cardiophyllum Lindl., and S. berthaultii Hawkes stood out at a high frequency of resistant accessions (7–9 points on a 9-point scale). Well-established specific SCAR markers of ten Rpi genes—Rpi-R1, Rpi-R2/Rpi-blb3, Rpi-R3a, Rpi-R3b, Rpi-R8, Rpi-blb1/Rpi-sto1, Rpi-blb2, and Rpi-vnt1—were used to mine 117 accessions representing 20 species from seven Petota series. In particular, our evidence confirmed the diverse Rpi gene location in two American continents. The structural homologs of the Rpi-R2, Rpi-R3a, Rpi-R3b, and Rpi-R8 genes were found in the North American species other than S. demissum, the species that was the original source of these genes for early potato breeding, and in some cases, in the South American Tuberosa species. The Rpi-blb1/Rpi-sto1 orthologs from S. bulbocastanum and S. stoloniferum Schlechtd et Bché were restricted to genome B in the Mesoamerican series Bulbocastana, Pinnatisecta, and Longipedicellata. The structural homologs of the Rpi-vnt1 gene that were initially identified in the South American species S. venturii Hawkes and Hjert. were reported, for the first time, in the North American series of Petota species.
Comparative Transcriptome Analysis Reveals the Interaction of Sugar and Hormone Metabolism Involved in the Root Hair Morphogenesis of the Endangered Fir Abies beshanzuensis
Authors: Liu Bin , Liu Ke , Chen Xiaorong , Xiao Duohong , Wang Tingjin , Yang Yang , Shuai Hui , Wu Sumei , Yuan Lu , Chen Liping
Published: January 2023

Abies beshanzuensis, an extremely rare and critically endangered plant with only three wild adult trees globally, is strongly mycorrhizal-dependent, leading to difficulties in protection and artificial breeding without symbiosis. Root hair morphogenesis plays an important role in the survival of mycorrhizal symbionts. Due to the lack of an effective genome and transcriptome of A. beshanzuensis, the molecular signals involved in the root hair development remain unknown, which hinders its endangered mechanism analysis and protection. Herein, transcriptomes of radicles with root hair (RH1) and without root hair (RH0) from A. beshanzuensis in vitro plantlets were primarily established. Functional annotation and differentially expressed gene (DEG) analysis showed that the two phenotypes have highly differentially expressed gene clusters. Transcriptome divergence identified hormone and sugar signaling primarily involved in root hair morphogenesis of A. beshanzuensis. Weighted correlation network analysis (WGCNA) coupled with quantitative real-time PCR (qRT-PCR) found that two hormone–sucrose–root hair modules were linked by IAA17, and SUS was positioned in the center of the regulation network, co-expressed with SRK2E in hormone transduction and key genes related to root hair morphogenesis. Our results contribute to better understanding of the molecular mechanisms of root hair development and offer new insights into deciphering the survival mechanism of A. beshanzuensis and other endangered species, utilizing root hair as a compensatory strategy instead of poor mycorrhizal growth.
A Review of Pistacia lentiscus Polyphenols: Chemical Diversity and Pharmacological Activities
Authors: Sehaki Chabha , Jullian Nathalie , Ayati Fadila , Fernane Farida , Gontier Eric
Published: January 2023

Pistacia lentiscus (lentisk) is a plant species of the Anacardiaceae family. It is a medicinal plant that grows wild in the Mediterranean region. This review aims to update the existing knowledge regarding P. lentiscus polyphenols by consulting references dated from 1996 to 2022. The data are organized and analyzed as follows: (i) to show the chemical diversity of phenolic products from P. lentiscus; (ii) to summarize the variability in phenolic composition and quantity; this could be attributed to plant origin, environmental conditions, phenological stage, and the polarity of the extraction solvents; (iii) to present the pharmacological properties in agreement with the traditional uses of this plant; and (iv) to demonstrate the correlation between the chemical profile and the pharmacological effect. Various compositions were observed, including phenolic acids, flavonoid glycosides, anthocyanins, catechins, and their derivatives. The biological and therapeutic potentials of lentisk extracts have been evaluated in terms of antioxidant, antimicrobial, and anti-inflammatory activities. Most of these activities are related to the phenolic composition of this plant. The content of this review will undoubtedly contribute to the choice of techniques for isolating the different bioactive molecules contained in the P. lentiscus. It is also of significance for the potential development of a micro-industrial sector based on the valorization of lentisk polyphenols.