Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review.

BACKGROUND: Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. CASE DESCRIPTION: Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. CONCLUSIONS: This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.

Insight into the potentiality of nano zero-valent iron on enhancing the nitrite accumulation and phosphorus removal performance of endogenous partial denitrification systems.

Endogenous partial denitrification (EPD) has drawn a lot of interest due to its abundant nitrite (NO2--N) accumulation capacity. However, the poor phosphate (PO43--P) removal rate of EPD restricts its promotion and application. In this study, the potentiality of various nano zero-valent iron (nZVI) concentrations (0, 20, 40, and 80 mg/L) on NO2--N accumulation and PO43--P removal in EPD systems had been investigated. Results showed that nZVI improved NO2--N accumulation and PO43--P removal, with the greatest nitrate-to-nitrite transformation ratio (NTR) and PO43--P removal rate of 97.74 % and 64.76 % respectively at the optimum nZVI level (80 mg/L). Microbial community analysis also proved that nZVI had a remarkable influence on the microbial community of EPD. Candidatus_Competibacter was contribute to NO2--N accumulation which was enriched from 24.74 % to 40.02 %. The enrichment of Thauera, Rhodobacteraceae, Pseudomonas were contributed to PO43--P removal. The chemistry of nZVI not only compensated for the deficiency of biological PO43--P removal, but also enhanced NO2--N enrichment. Therefore, nZVI had the huge potentiality to improve the operational performance of the EPD system.

Research Advances in Preparation, Stability, Application, and Possible Risks of Nanoselenium: Focus on Food and Food-Related Fields.

Nanoselenium is a promising selenium supplement as a result of its low toxicity and high bioavailability. However, the understanding on the preparation, stability, bioavailability, possible risks, and related underlying mechanisms of nanoselenium is not in-depth. Thus, the above aspects were reviewed on the basis of the latest literature. The reducing capacity and stability of the reducing agent and binding force between nanoselenium and the template decide the nanoselenium stability. Although research on nanoselenium application in food, agriculture, livestock, and aquaculture has been widely carried out, it is not widely applied in the fields. Se-containing amino acids are synthesized using nanoselenium adsorbed by organisms, and they constitute Se-containing proteins with other amino acids, which improves the health of organisms via scavenging excessive radicals. Notably, excessive nanoselenium intake generates redundant Se-containing amino acids, leading to dysfunction of key proteins in organisms, and its toxic doses vary with organisms. Furthermore, some issues related to nanoselenium still need to be solved urgently.

The Hidden Dangers of Plant-Based Diets Affecting Bone Health: A Cross-Sectional Study with U.S. National Health and Nutrition Examination Survey (NHANES) Data from 2005-2018.

The plant-based dietary pattern has been recommended for its potential health and environmental benefits, but its association with bone loss needs to be further explored. This study aimed to investigate the association between three plant-based diet indexes and bone loss in 16,085 adults, using data from the National Health and Nutrition Examination Survey. Three plant-based diet indexes (PDI, hPDI, and uPDI) were calculated from two NHANES 24-h dietary recall interviews, to characterize a plant-based diet. A multinomial logistic regression model was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). Higher hPDI and PDI were associated with increased risk of bone loss (ORQ5 vs. Q1 = 1.50; 95% CI: 1.24-1.81 for hPDI; ORQ5 vs. Q1 = 1.22; 95% CI: 1.03-1.45 for PDI), while higher uPDI was associated with increased risk of osteoporosis (ORQ5 vs. Q1 = 1.48; 95% CI: 1.04-2.11). A harmful association between plant-based diet indexes (hPDI and PDI) and osteopenia was observed at the lumbar spine rather than the femoral neck. We conducted several sensitivity analyses to ensure the robustness of results, including subgroup analysis, exclusion of people taking anti-osteoporotic and estrogenic drugs, further adjustment for menopausal status, corticosteroid usage, and dietary supplements, and calculation of E-value. Our study demonstrates the deleterious effects of a plant-based diet on bone health and emphasizes the importance of a balanced diet.

The function of omega-3 polyunsaturated fatty acids in response to cadmium exposure.

Throughout history, pollution has become a part of our daily life with the improvement of life quality and the advancement of industry and heavy industry. In recent years, the adverse effects of heavy metals, such as cadmium (Cd), on human health have been widely discussed, particularly on the immune system. Here, this review summarizes the available evidence on how Cd exposure may affect health. By analyzing the general manifestations of inflammation caused by Cd exposure, we find that the role of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in vivo can counteract Cd-induced harm. Additionally, we elucidate the effects of n-3 PUFAs on the immune system, and analyze their prophylactic and therapeutic effects on Cd exposure. Overall, this review highlights the role of n-3 PUFAs in the pathological changes induced by Cd exposure. Although n-3 PUFAs remain to be verified whether they can be used as therapeutic agents, as rehabilitation therapy, supplementation with n-3 PUFAs is reliable and effective.

Phytonanomaterials as therapeutic agents and drug delivery carriers.

Medicinal plants have been a major resource for drug discovery. Emerging evidence shows that in addition to pharmacologically active components, medicinal plants also contain phytochemical nanomaterials, or phytonanomaterials, which form nanoparticles for drug delivery. In this review, we examine the evidence supporting the existence of phytonanomaterials. Next, we review identification, isolation, and classification of phytonanomaterials, characteristics of phytonanomaterial-derived nanoparticles, and molecular mechanisms of phytonanomaterial assembly. We will then summarize the current progress in exploring phytonanomaterial-derived NPs as therapeutic agents and drug delivery carriers for disease treatment. Last, we will provide perspectives on future discovery and applications of phytonanomaterials.

A directed co-assembly of herbal small molecules into carrier-free nanodrugs for enhanced synergistic antitumor efficacy.

Carrier-free nanomedicines without structural modification are attractive for the development of natural small molecules (NSMs) and biomedical applications. Moreover, the combination of NSMs is expected to obtain nanomedicines with high efficacy and low side effects due to their inherent pharmacological activities and health benefits. However, poor water solubility and low bioavailability of NSMs limit their wider biomedical and clinical applications. In this study, we revealed the co-assembly properties of pentacyclic triterpenoids and constructed a series of carrier-free nanodrugs, which are co-assembled nanoparticles (NPs) formed by the combination of two NSMs via a supramolecular assembly strategy. Experimental work and simulation studies were combined to reveal the co-assembly mechanism of non-covalent interactions between NSMs. Not only do co-assembled NPs have rapid cellular uptake ability and passive targeting tumor ability based on the EPR effect, but also their constituent units could arrest the cell cycle at different stages of tumor cells and induce apoptosis, showing synergistic anti-tumor effects (CI < 0.7). Compared with self-assembled NPs and positive control, co-assembled NPs show the strongest therapeutic effect in vivo. Importantly, the co-assembled NPs highlight the unique advantages of NSMs in terms of biosafety and health benefits, and systemic toxicity and histological examination confirm that co-assembled NPs have reliable biosafety, and no side effects and nano toxicity risks were observed.

Retraction: A self-assembled supramolecular natural product gel from liquidambaric acid in traditional Chinese medicine with inherent anti-inflammatory activity for drug delivery.

Retraction for 'A self-assembled supramolecular natural product gel from liquidambaric acid in traditional Chinese medicine with inherent anti-inflammatory activity for drug delivery' by Kangkang Zhi et al., J. Mater. Chem. B, 2020, 8, 715-726, DOI: 10.1039/C9TB02416F.

Swietenine extracted from Swietenia relieves myocardial hypertrophy induced by isoprenaline in mice.

As a traditional plant medicine in tropical areas, Swietenia macrophylla seeds are usually applied for some chronic diseases, including hypertension, diabetes, and so on. Few studies have been carried out to identify the effective elements in seed extract and their indications. In this study, we first investigated the functions of the swietenine, an extract from S. macrophylla seeds, using a model of myocardial hypertrophy induced by isoprenaline (ISO). At cellular level, H9c2 cell hypertrophy was also established through the treatment with ISO. The cardiac pathological remodeling was evaluated by echocardiography and histological analysis. Western blot and RT-qPCR were used to detect the expression of possible hypertrophy-promoting genes. Here, our results indicated that swietenine remarkably attenuated ISO-induced myocardial hypertrophy in vivo and in vitro. Moreover, Akt phosphorylation, ANP and BNP mRNA expression were efficiently decreased. Based on these findings, we concluded that swietenine might be a promising anti-hypertrophic agent against cardiac hypertrophy.

A self-assembled supramolecular natural product gel from liquidambaric acid in traditional Chinese medicine with inherent anti-inflammatory activity for drug delivery.

Self-assembled supramolecular gels as a soft material have received extensive attention due to their excellent physicochemical properties such as variability, multiple responsiveness and appropriate viscoelasticity. At present, many self-assembled gels with physicochemical functions are constructed as drug delivery systems and used for the treatment of diseases. However, self-assembled gel drug delivery systems having pharmacological functions remain almost unexplored. Here, we present an anti-inflammatory pharmacologically active gel drug delivery system consisting of direct self-assembled small molecule naturally-occurring compounds (self-assembled small molecule natural products, SSNPs) derived from traditional Chinese medicine. The system not only exhibits excellent thixotropy, good topical safety and sustained release, but also achieves superior inflammatory therapeutic effects both in vivo and in vitro. Compared to non-pharmacologically active drug delivery systems, this system can increase the in vivo anti-inflammatory activity of drugs by nearly two-thirds. More importantly, its therapeutic effect even reached 141.54% of OTC drugs. The successful construction of an anti-inflammatory pharmacologically active gel drug delivery system not only makes full use of the self-assembly properties and biological activity of natural products, but also provides an important reference for the development of pharmacologically active drug delivery systems using SSNPs in the future.

Neferine suppresses osteoclast differentiation through suppressing NF-κB signal pathway but not MAPKs and promote osteogenesis.

Osteoporosis is an ageing disease characterized by elevated osteoclastic bone resorption resulting in bone loss, decrease bone strength, and elevated incidence of fractures. Neferine, a natural compound isolated from the traditional Chinese medicine Nelumbo nucifera (Lotus), has been reported exhibit anti-inflammatory, antioxidant, and anticancer properties. However, its effect on bone remains to be determined. Here we showed that Neferine inhibits RANKL-induced osteoclast formation in a dose- and time-dependent manner. Furthermore, Neferine also demonstrated antiresorptive properties by effectively ameliorating the bone resorptive activity of mature osteoclasts. Mechanistically, Neferine suppressed RANKL-induced activation of NF-κB signaling pathway. This in turn hindered the induction and activation of NFATc1 resulting in downregulation of osteoclast marker genes closely related to differentiation, fusion as well as bone resorption. Interestingly, we found Neferine enhanced the differentiation and bone mineralization activity of MC3T3-E1 preosteoblast cells. Finally, mice treated with Neferine was protected against ovariectomy (OVX)-induced bone loss. The Neferine treatment improved bone volume following ovariectomy and also exhibited less TRAP-positive osteoclasts on bone surface. Collectively our data provide promising evidence that Neferine could be a potential therapeutic application for against osteolytic bone conditions such as osteoporosis.

Single small molecule-assembled nanoparticles mediate efficient oral drug delivery.

Oral drug delivery, which requires surviving the harsh environment in the gastrointestinal (GI) tract and penetrating the intestinal epithelium, has not been achieved using simple formulation nanoparticles (NPs). Medicinal natural products (MNPs) have been widely used in traditional medicine for disease management through oral consumption. However, most pharmacologically active compounds within MNPs do not have the properties suitable for oral applications. We hypothesize that some MNPs contain natural nanomaterials that can convert those compounds into oral formulations by forming NPs. After screening 66 MNPs, we identified five classes of small molecules that form NPs, many of which are capable of efficient drug encapsulation and GI penetration. We show that one of them, dehydrotrametenolic acid (DTA), is capable of mediating oral delivery for effective disease treatment. We determine that DTA NPs assemble through hydrogen bonding and penetrate the GI tract via apical sodium-dependent bile acid transporter. Our study reveals a novel class of single component, small molecule- assembled NPs for oral drug delivery, and suggests a novel approach to modernizing MNPs through nanomaterial discovery.

[Determination of nerolidol in volatile oil of Dalbergia odorifera by GC].

OBJECTIVE: To develop a method for determination of nerolidol in the volatile oil of Dalbergia odorifera. METHOD: GC method was used. The samples were separated on Agilent HP-5 column (320 microm x 30 m, 0.25 microm) with the mobile phase of highly pure N2. Flow rate was 2 mL x min(-1). RESULT: Linearity of nemlidol was good linearity in the range of 0.059-1.97 mg x mL(-1), and the average recovery was 97.5%, RSD 2.3%. CONCLUSION: This method is simple, accurate, rapid and reproducible.