Efficacy of Fire-Needle Therapy in Improving Neurological Function Following Cerebral Infarction and Its Effect on Intestinal Flora Metabolites.

Objective: This study was to investigate the mechanism of action and clinical efficacy of fire-needle therapy in improving neurological function in patients with acute cerebral infarction (identified as a wind-phlegm-blood stasis syndrome in traditional Chinese medicine). Methods: We included patients diagnosed with acute cerebral infarction (wind-phlegm-blood stasis syndrome) admitted to the Encephalopathy and Acupuncture Center of the Second Affiliated Hospital of Tianjin University of Chinese Medicine. We randomly allocated them into the treatment and control groups, with 45 cases in each group. Acupuncture treatments that focused on regulating the mind and dredging the collaterals were used in the control group, while the treatment group additionally received fire-needle therapy. Our indicators included the National Institutes of Health Stroke Scale (NIHSS) scores, the Fugl-Meyer Assessment (FMA) scale, peripheral blood tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), hypersensitivity C-reactive protein (hs-CRP), and intestinal metabolites short-chain fatty acids (SCFAs). We measured these indicators before treatment and 14 days after treatment. Results: The post-treatment NIHSS scores of the two groups were significantly reduced (P < 0.05), and the treatment group showed a more significant decline in the score when compared to the control group (P < 0.05). The treatment group showing significant improvement in the domains of reflex activity, mobility, cooperative movement, and finger movement (P < 0.05). Both groups showed a significant decrease in the IL-17 and hs-CRP levels (P < 0.05), with the treatment group demonstrating a significant declining trend when compared to the control group (P < 0.05). The levels of acetic acid, propionic acid, butyric acid, and valeric acid all increased significantly in the two groups (P < 0.05), with acetic acid and butyric acid increasing significantly in the treatment group when compared to the control group (P < 0.05). Clinical efficacy rate: 78.6% of patients in the treatment group had an excellent rate, whereas it was 30.0% in the control group, and the difference was statistically significant (P < 0.001). Conclusion: Fire-needle therapy was effective in upregulating the SCFA content in patients with acute cerebral infarction (wind-phlegm-blood stasis syndrome), inhibiting the level of the inflammatory response, and improving the recovery of neurological functions. Clinical registration number: Registration website link: https://www.chictr.org.cn. Registration date: 2022/9/27. Registration number: ChiCTR2200064122.

[Retracted] CCL26 regulates the proportion of CD4+CD25+FOXP3+ Tregs and the production of inflammatory factors in peripheral blood mononuclear cells following acute ischemic stroke via the STAT5 pathway.

[This retracts the article DOI: 10.3892/etm.2020.9046.].

Regulation of Stem Cell Differentiation by Inorganic Nanomaterials: Recent Advances in Regenerative Medicine.

Transplanting stem cells with the abilities of self-renewal and differentiation is one of the most effective ways to treat many diseases. In order to optimize the therapeutic effect of stem cell transplantation, it is necessary to intervene in stem cell differentiation. Inorganic nanomaterials (NMs), due to their unique physical and chemical properties, can affect the adhesion, migration, proliferation and differentiation of stem cells. In addition, inorganic NMs have huge specific surface area and modifiability that can be used as vectors to transport plasmids, proteins or small molecules to further interfere with the fate of stem cells. In this mini review, we summarized the recent advances of common inorganic NMs in regulating stem cells differentiation, and the effects of the stiffness, size and shape of inorganic NMs on stem cell behavior were discussed. In addition, we further analyzed the existing obstacles and corresponding perspectives of the application of inorganic NMs in the field of stem cells.

Biomimetic Black Phosphorus Nanosheet-Based Drug Delivery System for Targeted Photothermal-Chemo Cancer Therapy.

As a biodegradable material, black phosphorus (BP) has been considered as an efficient agent for cancer photothermal therapy. However, its systemic delivery faces several hurdles, including rapid degradation in blood circulation, quick clearance by the immune system, and low delivery sufficiency to the tumor site. Here, we developed a biomimetic nanoparticle platform for in vivo tumor-targeted delivery of BP nanosheets (BP NSs). Through a biomimetic strategy, BP NSs were utilized to coordinate with the active species of oxaliplatin (1,2-diaminocyclohexane) platinum (II) (DACHPt) complexions, and the nanoparticles were further camouflaged with mesenchymal stem cell (MSC)-derived membranes. We showed that the incorporation of DACHPt not only decelerated the BP degradation but also enhanced the antitumor effect by combining the photothermal effect with chemotoxicity. Furthermore, MSC membrane coating increased the stability, dispersibility, and tumor-targeting properties of BP/DACHPt, significantly improving the antitumor efficacy. In short, our work not only provided a new strategy for in vivo tumor-targeted delivery of BP NSs but also obtained an enhanced antitumor effect by combining photothermal therapy with chemotherapy.

CCL26 regulates the proportion of CD4+CD25+FOXP3+ Tregs and the production of inflammatory factors in peripheral blood mononuclear cells following acute ischemic stroke via the STAT5 pathway.

Acute ischemic stroke (AIS) is the most common type of stroke. Recent studies have found that AIS is closely involved in the immune regulation function of regulatory T cells (Tregs). C-C motif chemokine ligand 26 (CCL26) is a member of the chemokine family that plays an essential role in cell activation, cell differentiation, lymphocyte homing, and inflammatory and immune responses. The present study aimed to investigate the role of CCL26 in the regulation of Tregs in AIS. Peripheral blood mononuclear cells (PBMCs) were incubated with a CCL26-neutralizing antibody. The proportion of cluster of differentiation (CD)4+CD25+ forkhead box P3 (FOXP3)+ Tregs was increased, and the expression of FOXP3, phosphorylated signal transducer and activator of transcription 5 (p-STAT5), and that of the immunosuppressive factors, interleukin (IL)-10 and transforming growth factor (TGF)-ß1, was upregulated. Conversely, the expression of immune-promoting factors, such as tumor necrosis factor (TNF)-α and IL-6 was significantly downregulated. Further experiments using CCL26 recombinant protein-treated PBMCs revealed a decreased proportion of CD4+CD25+FOXP3+ Tregs and the downregulated expression of FOXP3, p-STAT5, TGF-ß1 and IL-10. Moreover, the expression of immunostimulatory factors, such as CX3C chemokine receptor 1, TNF-α and IL-6 was significantly upregulated. On the whole, these results demonstrate that CCL26 regulates the proportion of CD4+CD25+FOXP3+ Tregs and the production of inflammatory factors in PBMCs following AIS via the STAT5 pathway.

A novel method for salts removal from municipal solid waste incineration fly ash through the molten salt thermal treatment.

The disposal of the hazardous municipal solid waste (MSW) incineration fly ash is a critical environmental issue in China and the high contents of salts in the fly ash make the ash disposal extremely difficult. The present study proposes a novel method for the salts removal from MSW incineration fly ash using molten carbonates and chlorides at moderate temperatures from 773 K to 1073 K. The results showed that molten salts could effectively extract alkali and alkaline earth metals chlorides and sulfates from the fly ash. Other ash components, like Si/Al-compounds, were precipitated from the molten salts and concentrated in residues. By comparison, molten carbonates showed greater capability in the salts extraction while molten chlorides showed better selectivity in chlorides removal from MSW incineration fly ash. These findings suggest that the optimization of molten salts system could further prove the potential applicability of molten salts thermal treatment method for the salts removal from MSW incineration fly ash.

An enzyme-free strategy for ultrasensitive detection of adenosine using a multipurpose aptamer probe and malachite green.

We report on an enzyme-free and label-free strategy for the ultrasensitive determination of adenosine. A novel multipurpose adenosine aptamer (MAAP) is designed, which serves as an effective target recognition probe and a capture probe for malachite green. In the presence of adenosine, the conformation of the MAAP is converted from a hairpin structure to a G-quadruplex. Upon addition of malachite green into this solution, a noticeable enhancement of resonance light scattering was observed. The signal response is directly proportional to the concentration of adenosine ranging from 75 pM to 2.2 nM with a detection limit of 23 pM, which was 100-10,000 folds lower than those obtained by previous reported methods. Moreover, this strategy has been applied successfully for detecting adenosine in human urine and blood samples, further proving its reliability. The mechanism of adenosine inducing MAAP to form a G-quadruplex was demonstrated by a series of control experiments. Such a MAAP probe can also be used to other strategies such as fluorescence or spectrophotometric ones. We suppose that this strategy can be expanded to develop a universal analytical platform for various target molecules in the biomedical field and clinical diagnosis.

Dual-channel detection of metallothioneins and mercury based on a mercury-mediated aptamer beacon using thymidine-mercury-thymidine complex as a quencher.

A novel dual-channel strategy for the detection of metallothioneins (MTs) and Hg(2+) has been developed based on a mercury-mediated aptamer beacon (MAB) using thymidine-mercury-thymidine complex as a quencher for the first time. In the presence of Hg(2+), the T-rich oligonucleotide with a 6-carboxyfluorescein (TRO-FAM) can form an aptamer beacon via the formation of T-Hg(2+)-T base pairs, which results in a fluorescence quenching of the sensing system owing to the fluorescence resonance energy transfer (FRET) from the fluorophore of FAM to the terminated T-Hg(2+)-T base pair. The addition of MTs into this solution leads to the disruption of the T-Hg(2+)-T complex, resulting in an increase of the fluorescent signal of the system. In the optimizing condition, ΔF was directly proportional to the concentrations ranging from 5.63 nM to 0.275 µM for MTs, and 14.2 nM to 0.30 µM for Hg(2+) with the detection limits of 1.69 nM and 4.28 nM, respectively. The proposed dual-channel method avoids the label steps of a quencher in common molecular beacon strategies, without tedious procedure or the requirement of sophisticated equipment, and is rapid, inexpensive and sensitive.

Ultrasensitive detection of uranyl by graphene oxide-based background reduction and RCDzyme-based enzyme strand recycling signal amplification.

We proposed a novel strategy which combines graphene oxide-based background reduction with RCDzyme-based enzyme strand recycling amplification for ultrahigh sensitive detection of uranyl. The RCDzyme is designed to contain a guanine (G)-rich sequence that replaces the partial sequence in an uranyl-specific DNAzyme. This multifunctional probe can act as the target recognition element, DNAzyme and the primer of signal amplification. The presence of UO2(2+) can induce the cleavage of the substrate strands in RCDzyme. Then, each released enzyme strand can hybridize with another substrate strands to trigger many cycles of the cleavage by binding uranyl, leading to the formation of more G-quadruplexes by split guanine-rich oligonucleotide fragments. The resulting G-quadruplexes could bind to N-methyl-mesoporphyrin IX (NMM), causing an amplified detection signal for the target uranyl. Next, graphene oxide-based background reduction strategy was further employed for adsorbing free ssDNA and NMM, thereby providing a proximalis zero-background signal. The combination of RCDzyme signal amplification and proximalis zero-background signal remarkably improves the sensitivity of this method, achieving a dynamic range of two orders of magnitude and giving a detection limit down to 86 pM, which is much lower than those of related literature reports. These achievements might be helpful in the design of highly sensitive analytical platform for wide applications in environmental and biomedical fields.

A novel strategy for dual-channel detection of metallothioneins and mercury based on the conformational switching of functional chimera aptamer.

A novel strategy for dual-channel detection of metallothioneins (MTs) and Hg(2+) has been proposed. In the absence of Hg(2+), the functional chimera aptamer (FCA) designed can form an intact G-quadruplex with flexibility, which was demonstrated to have peroxidase-like activities upon hemin binding. In the presence of Hg(2+), the formation of T-Hg(2+)-T complex results in the conformational switching of FCA, which lost the peroxidase-like activities and cannot catalyze the oxidation of ABTS by H2O2. Upon addition of MTs in this solution, MTs could interact with Hg(2+) to form a MTs-Hg(2+) complex, leading to the recovery of the G-quadruplex DNAzyme. The color and absorbance of the sensing system were also changed accordingly. In the optimizing condition, ΔA was directly proportional to the concentration ranging from 8.84 nM to 1.0 µM for Hg(2+), and 7.82 nM to 0.462 µM for MTs with the detection limits of 2.65 nM and 2.34 nM, respectively. The proposed dual-channel method avoids the label steps in common methods, and allows direct analysis of the samples without costly instruments, and is reliable, inexpensive and sensitive.

A colorimetric aptasensor for the highly sensitive detection of 8-hydroxy-2'-deoxyguanosine based on G-quadruplex-hemin DNAzyme.

A highly sensitive, low-cost colorimetric aptasensor was developed for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human urine. The method is based on a conformational switching of the 8-OHdG aptamer to form a G-quadruplex structure in the presence of 8-OHdG. The resulting G-quadruplex assembles into a peroxidase-like DNAzyme with hemin, which effectively catalyzes the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS(2-)) by H2O2 to ABTS(+), resulting in an increase in the absorption signal at 416nm along with a color change of the solution. The response signals linearly correlated with the concentration of 8-OHdG, ranging from 466pM to 247nM with a detection limit of 141pM. The relative standard deviation and the recovery were 1.97-3.47% (n=11) and 98.8-100.2%, respectively. The proposed method avoids the label and derivatization steps in common methods and allows direct analysis of the samples by the naked eye without costly instruments, which is reliable, inexpensive, and sensitive.