POEMS syndrome with undetectable M-protein: a case report and literature review.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. CASE PRESENTATION: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. CONCLUSIONS: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

Effects of cadmium and zinc interactions on the physiological biochemistry and enrichment characteristics of Iris pseudacorus.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

Recent advancements with loop-mediated isothermal amplification (LAMP) in assessment of the species authenticity with meat and seafood products.

Species adulteration or mislabeling with meat and seafood products could negatively affect the fair trade, wildlife conservation, food safety, religion aspect, and even the public health. While PCR-based methods remain the gold standard for assessment of the species authenticity, there is an urgent need for alternative testing platforms that are rapid, accurate, simple, and portable. Owing to its ease of use, low cost, and rapidity, LAMP is becoming increasingly used method in food analysis for detecting species adulteration or mislabeling. In this review, we outline how the features of LAMP have been leveraged for species authentication test with meat and seafood products. Meanwhile, as the trend of LAMP detection is simple, rapid and instrument-free, it is of great necessity to carry out end-point visual detection, and the principles of various end-point colorimetry methods are also reviewed. Moreover, with the aim to enhance the LAMP reaction, different strategies are summarized to either suppress the nonspecific amplification, or to avoid the results of nonspecific amplification. Finally, microfluidic chip is a promising point-of-care method, which has been the subject of a great deal of research directed toward the development of microfluidic platforms-based LAMP systems for the species authenticity with meat and seafood products.

Sonic hedgehog-heat shock protein 90ß axis promotes the development of nonalcoholic steatohepatitis in mice.

Sonic hedgehog (SHH) and heat shock protein 90ß (HSP90ß) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90ß is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90ß ubiquitylation through deubiquitylase USP31, thus preventing HSP90ß degradation and promoting hepatic lipid synthesis. HSP90ß significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90ß axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90ß-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.

Development of a one-pot and sequence-specific LAMP assay based on the self-quenching probe integrated by the complementary oligonucleotide for an enhanced fluorescence quenching.

Single-modified fluorogenic primer (Sfp) enables accurate identification of LAMP amplicons without being affected by non-specific products. However, the fluorescence self-quenching by nucleobases for Sfp is generally of low efficiency, and the high background signal makes it a great challenge to achieve visual inspection with naked eyes. In the present study, the oligonucleotide (Ao) complementary to Sfp was designed, which would hybridize to Sfp and dramatically heighten the quenching effect, leading to a low background signal in negative reaction. Instead, for positive reaction, Sfp is incorporated into the double-stranded amplicons, resulting in dequenching and consequently, enhanced fluorescence. The detection scheme can be further improved by a dual-color fluorescence strategy, allowing visual detection of 1 pg rainbow trout DNA in a closed-tube format within 30 min. Therefore, our LAMP-Ao-Sfp assay represents a useful tool for rapid and sensitive detection, and can serve as a reliable method for on-site detection in low-resource settings.

Fish species mislabelling in China: evidence from a survey of frozen, dried, and surimi-based fish products marketed as cod-related species.

'Cod'-related species are among the most appreciated marine fish resources around the world, but are also prone to species mislabelling. In the present study, a total of 76 frozen, dried, and surimi-based fish products, sold as 'Cod' (59 products), 'Atlantic authentic Cod' (11 products), and 'Authentic Cod' (6 products), were collected in China. A species-specific LAMP (loop-mediated isothermal amplification) method was used to screen for the presence of Atlantic cod (Gadus morhua), Pacific cod (G. macrocephalus), Alaska pollock (G. chalcogrammus), Southern hake (Merluccius australis), which was cross-confirmed using real-time PCR and DNA sequencing methods. The results highlighted the greatest species diversity for 'Cod' products, and the identified species were from nine different families. It appears that the practice of assigning a specific type or category of species to the common name 'Cod' has not been widely advocated, and the misuse of this ambiguous common name has been a common practice for species adulteration, negatively impacting consumers' rights and marine conservation. To rebuild consumers' confidence, retail fish suppliers have differentiated their products by adding specific qualifiers in front of the common name 'Cod' on the label, such as 'Authentic cod' and 'Atlantic authentic cod'. The endeavour is highly meaningful, since Gadus morhua was identified as the species for a significant majority of 'Atlantic authentic cod' and 'Authentic cod' products (64.7%, 11/17), with the remaining six products identified as Alaskan pollock (G. chalcogrammus), Pacific cod (G. macrocephalus) and North Pacific hake (Merluccius productus). Despite the positive effort to reverse species mislabelling from retail on-line fish suppliers, a standardized fish nomenclature stipulated by the responsible authorities remains crucial for enhancing transparency and continuing to reduce species mislabelling.

A rapid and closed-tube method based on the dual-color fluorescence loop-mediated isothermal amplification for visual detection of Atlantic salmon (Salmo salar).

Loop-mediated isothermal amplification (LAMP) visual detection based on hydroxyl naphthol blue (HNB) and SYTO 9 is often confounded by the narrow color variation window and the requirement of empirical preset of cutoff intensity value. To improve the suitability for naked-eye inspection, the present work proposed a strategy based on the fluorescence property of SYTO 9 and HNB to enlarge the contrast and a novel dual-color fluorescence LAMP (dfLAMP) assay was developed for visual detection of Atlantic salmon. Specifically, HNB of 26.25 µM, blended with SYTO 9 of 0.75-1.5 µM, was added in the mixture before amplification, producing light green fluorescence for both positive and negative samples. After amplification, green or yellow-green fluorescence was observed for positive samples, while only orange-red fluorescence emitted for negative ones, enabling an easy and rapid distinguish. The optimized dfLAMP assay has proved its specificity and can detect as little as 1 fg Atlantic salmon DNA.

7-aminocephalosporanic acid, a novel HSP90ß inhibitor, attenuates HFD-induced hepatic steatosis.

Hepatic steatosis is one of the most important causes of liver disease worldwide. Heat shock protein 90 (HSP90) is essential for numerous client proteins. Recently, more attention was focused on increased HSP90 levels in hepatic steatosis, especially HSP90ß. Thus, great efforts have been made to develop HSP90ß inhibitors, and most natural inhibitors are derived from microorganisms. In this study, using microarray chips and surface pasmon resonance (SPR) technology, we screened 189 antibiotics in order to obtain an inhibitor directly binding to the non-N-terminal domain of HSP90ß. Finally, we discovered an antibiotic, 7-aminocephalosporanic acid (7ACA), with a KD value of 6.201 µM between 7ACA and non-N-terminal domain of HSP90ß. Besides, 7ACA was predicted to interact with the middle domain (MD) of HSP90ß. In HepG2 cells, we found that 7ACA reduced cellular total cholesterol (TC) and triglyceride (TG) by decreasing sterol regulatory element-binding proteins (SREBPs). In HFD fed mice, administration of 7ACA (5, 10, and 25 mg kg-1 d-1, ig, for 12 weeks) dose-dependently decreased serum TC and TG and played an important role in protecting liver and adipose tissue from lipid accumulation. In conclusion, our study demonstrated that antibiotic 7ACA, as an HSP90ß middle domain inhibitor, was promising for the development of lipid-lowering drugs.

Visual detection of rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) simultaneously by duplex loop-mediated isothermal amplification.

Loop-mediated isothermal amplification (LAMP) is often confounded by the non-specific amplification arising from primer dimers, off-target priming, and other artifacts. Precipitation of the DNA produced during LAMP with the use of specific fluorescently labeled probe has proved the effectiveness in specific detection. Herein, two fluorophores (ROX and FAM) were attached to the primers S-LB-6 and R-FIP for Atlantic salmon and rainbow trout, respectively, which are self-quenched in unbound state and become de-quenched after binding to the dumbbell-shaped DNA specifically. The DNA precipitation and appearance of small sediment took 10 s of centrifugation at 1000 g, by adding polyethylenimine (PEI) 600. Each target species was specifically amplified with the predicted color of PEI-DNA sediment, namely red for Atlantic salmon, green for rainbow trout, and pale yellow for mixed species. The optimized duplex LAMP system has proved its specificity and can detect as little as 1 ng DNA in visual detection.

Establishment of a rapid method for skipjack tuna (Katsuwonus pelamis) authentication using molecular beacons in loop-mediated isothermal amplification.

One major drawback to the traditional loop-mediated isothermal amplification (LAMP) detection methods is the increased likelihood of detecting false-positive signals derived from non-specific amplification. Molecular beacon (MB) is increasingly being used in many applications and the MB-LAMP assay has proved itself as a target-specific method. The present work selected skipjack tuna as a case study, and developed a novel MB-LAMP assay for rapid species authentication. Specifically, the optimal MB structure includes 13 nucleobases in the loop region (binding specifically to loop primer LF) and 5 nucleobases in the stem region. For the established MB-LAMP assay, in the presence of the amplicons, the MB probe LFP-1 hybridizes to its target and forms a double helix. The change in conformation separates the quencher from the fluorophore, thereby resulting in the fluorescence release. The novel MB-LAMP assay has proved its specificity and can detect as little as 0.5 pg of skipjack tuna DNA.

Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives to reduce SREBPs expression for the treatment of hyperlipidemia.

Statins play an important role in the treatment of hyperlipidemia, but drug resistance and adverse effects greatly limits their application. To discover new lipid-lowering drugs, three different series of tetrahydroprotoberberine derivatives (THPBs) were designed and synthesized. These compounds were first tested for their effects on viability of HepG2 cells and 21 compounds with the percent of cell viability over 90% were further screened to evaluate their ability to reduce total cholesterol (TC) and triglyceride (TG) levels. Among these derivatives, two compounds displayed significant down-regulation both intracellular of TC and TG content, especially compound 49 exhibited the greatest efficacy. Mechanistically, compound 49 promoted proteasomal degradation of SREBPs. Importantly, compound 49 displayed superior bioavailability (F = 65.1%) and obvious efficacy in the treatment of high fat diet induced obesity in vivo. Therefore, compound 49 is a promising candidate to develop new treatment of hyperlipidemia.

A novel colorimetric and fluorometric probe for biothiols based on MnO2 NFs-Rhodamine B system.

Herein, a novel bimodal ratiometric probe for sensitive and selective detection of biothiols (including glutathione (GSH), cysteine (Cys) and homocysteine (Hcys)) was constructed, which was based on the redox reaction between manganese dioxide nanoflakes (MnO2 NFs) and rhodamine (RhB) and biothiols. When MnO2 NFs was added into RhB solution, RhB was oxidized to a series of derivatives, accompanying with the colorimetric color changing from purple to light pink and fluorescence changing from red to green. In the presence of GSH, Cys or Hcys, they could reduce MnO2 NFs to Mn2+, thereby preventing the following oxidization of RhB and the corresponding color and fluorescence changes. The absorption intensity ratio and fluorescence intensity ratio showed good linear relationships with the concentrations of biothiols. The colorimetric detection limits for GSH, Cys and Hcys were 0.057 µM, 0.140 µM and 0.087 µM, respectively. And the fluorescence detection limits were 0.177 µM, 0.282 µM and 0.161 µM. More importantly, this probe was successfully applied to monitor the concentration of GSH/Cys/Hcys in human serum samples, with satisfactory recovery. Thus, this MnO2 NFs-RhB platform can potentially be a candidate for the detection of biothiols.

Visual and fluorescent detection of mercury ions using a dual-emission ratiometric fluorescence nanomixture of carbon dots cooperating with gold nanoclusters.

Mercury (II) ions (Hg2+), as one of the most toxic heavy metals, can cause irreversible damage to human health even at very low concentration due to its high toxicity and bioaccumulation. Herein, a facile ratiometric fluorescence nanomixture based on carbon dots­gold nanoclusters (CDs-Au NCs) was constructed for quantitative detection of Hg2+. Lysine functionalized carbon dots (CDs) were prepared by one-pot hydrothermal method, while gold nanoclusters (Au NCs) were synthesized via using chicken egg white (CEW) as reducer and stabilizer. The novel nanomixture exhibited two strong emission peaks at 450 nm and 665 nm under 390 nm excitation, and showed pink fluorescence under UV light. Interestingly, the fluorescence of the CDs-Au NCs nanomixture was selectively response to Hg2+. The fluorescence of Au NCs at 665 nm was decreased when Hg2+ was presented in the solution, while the fluorescence of CDs at 450 nm stayed constant. The fluorescence color changed from pink to blue obviously with increasing the concentration of Hg2+, which indicated that CDs-Au NCs could be used for visual detection Hg2+ by the naked eye. Under optimal conditions, this ratiometric fluorescent sensor could detect Hg2+ accurately and possess a great sensitivity with a detection limit of 63 nM. In addition, this method was applied to detect Hg2+ in real water samples with great recoveries, suggesting its potential in practical application with simplicity, environmentally friendly and low cost.

Molecular engineering of a colorimetric two-photon fluorescent probe for visualizing H2S level in lysosome and tumor.

As a multifunctional signaling molecule, hydrogen sulfide (H2S) plays an essential role in diverse physiological and pathological processes. The two-photon fluorescence probes detecting H2S selectively in vivo could be useful tools to better study the mechanism of diseases. Then, an efficient two-photon lysosome-specific probe 1 has been developed to detect endogenous H2S in living cells and mice. Probe 1 displays excellent properties with 28-fold fluorescence enhancement, marked color changes in naked-eye and fluorescence, high selectivity and sensitivity, and low detection limit (0.22 µM) to H2S. These remarkable properties of probe 1 enable its practical applications in detecting H2S in environment (wastewater) and food (beer). Moreover, as a two-photon probe under near infrared excitation at 790 nm, probe 1 can monitor the level changes of endogenous H2S of lysosome and tumor in living system with good membrane permeability and high imaging resolution. Specially, the probe detecting H2S distribution in lysosome could provide more evidences to explain the association of target-organelle and H2S.

Carbon quantum dot-based fluorometric nitrite assay by exploiting the oxidation of iron(II) to iron(III).

The authors describe a simple and economical fluorescence method for the determination of nitrite by utilizing the fact that nitrite possesses strong oxidation in acidic solution and is capable to transform iron(II) into iron(III) ions. The latter quenches the fluorescence of carbon quantum dots (CQDs) based on the fluorescence static and dynamic quenching effect. The optimum reaction conditions and other analytical parameters are investigated to enhance the sensitivity of the method. At the excitation wavelength of 360 nm, this probe has a linear response in the 10 to 400 µM nitrite concentration range, with a correlation coefficient of R2 = 0.9958 (n = 3) and a detection limit of 0.48 µM. This method was successfully applied to the determination of nitrite in three different sausage samples and gave recoveries in the range between 101.8 to 103.0%, demonstrating the accuracy, reliability and potential application of this assay for monitoring nitrite. Graphical Abstract The carbon quantum dot/iron(II) ions system was used for the fluorometric detection of nitrite in food and environmental water. This probe exploits the oxidizing property of nitrite in acidic solution. Iron(II) is oxidized to iron(III) which exerts a strong fluorescence quenching effect.