Melatonin reverses type 2 diabetes-induced cognitive deficits via attenuation of oxidative/nitrosative stress and NF-κB-mediated neuroinflammation in rat hippocampus

Purpose: To evaluate the protective effect of melatonin on diabetes-induced cognitive dysfunction. Methods: Rats were fed a high-fat diet + streptozotocin (HFD + STZ) for 15 weeks to induce type 2 diabetes (HFD + STZ group). At the end of the 15-week induction of diabetes, cognitive function in the diabetic rats was estimated using a Morris water maze and an object recognition task. Next, the diabetic rats were treated with melatonin (10 mg/ kg, po) for 3 weeks. Thereafter, cognitive function was reevaluated in the melatonin-treated diabetic rats (melatonin group). Results: There was a significant (p < 0.01) decrease in the serum glucose and insulin in melatonintreated diabetes type 2 rats compared with that of diabetes type 2 rats exposed to only HFD + STZ. Treatment with melatonin (10 mg/kg, po) for 3 weeks in diabetic type 2 rats also caused a significant increase (p < 0.01) in the time spent in the target quadrant and preference index in diabetic rats compared with the HFD + STZ group. There were significant decreases in reactive oxygen species (ROS), oxido-nitrosative stress markers, including thiobarbituric acid reactive substances (TBARS), nitrite, and depleted glutathione (GSH) level in the hippocampus of melatonin-treated group, compared with the HFD + STZ-treated group. Moreover, the melatonin-treated group showed significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and reduction in the levels of proinflammatory cytokines. Conclusion: The results demonstrate that melatonin prevents cognitive dysfunction in type 2 diabetic rats by attenuating oxido-nitrosative stress and NF-κB-mediated neuroinflammation. This effect suggests that melatonin may be useful for the management of cognitive dysfunction in patients suffering from diabetes. Keywords: Cognitive dysfunction, Melatonin, Neuroinflammation, Nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB), Oxido-nitrosative stress, Type 2 diabete

Impaired function of dendritic cells within the tumor microenvironment

Dendritic cells (DCs), a class of professional antigen-presenting cells, are considered key factors in the initiation and maintenance of anti-tumor immunity due to their powerful ability to present antigen and stimulate T-cell responses. The important role of DCs in controlling tumor growth and mediating potent anti-tumor immunity has been demonstrated in various cancer models. Accordingly, the infiltration of stimulatory DCs positively correlates with the prognosis and response to immunotherapy in a variety of solid tumors. However, accumulating evidence indicates that DCs exhibit a significantly dysfunctional state, ultimately leading to an impaired anti-tumor immune response due to the effects of the immunosuppressive tumor microenvironment (TME). Currently, numerous preclinical and clinical studies are exploring immunotherapeutic strategies to better control tumors by restoring or enhancing the activity of DCs in tumors, such as the popular DC-based vaccines. In this review, an overview of the role of DCs in controlling tumor progression is provided, followed by a summary of the current advances in understanding the mechanisms by which the TME affects the normal function of DCs, and concluding with a brief discussion of current strategies for DC-based tumor immunotherapy

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values

Measurement of the cross section of e+e−→Ξ−Ξˉ+e^+e^-\rightarrow\Xi^{-}\bar\Xi^{+} at center-of-mass energies between 3.510 and 4.843 GeV

Using $e^+e^-$ collision data corresponding to a total integrated luminosity of 12.9 $fb^{-1}$ collected with the BESIII detector at the BEPCII collider, the exclusive Born cross sections and the effective form factors of the reaction $e^+e^-\rightarrow\Xi^{-}\bar\Xi^{+}$ are measured via the single baryon-tag method at 23 center-of-mass energies between 3.510 and 4.843 GeV. Evidence for the decay $\psi(3770)\rightarrow\Xi^{-}\bar\Xi^{+}$ is observed with a significance of 4.5$\sigma$ by analyzing the measured cross sections together with earlier BESIII results. For the other charmonium(-like) states $\psi(4040)$, $\psi(4160)$, $Y(4230)$, $Y(4360)$, $\psi(4415)$, and $Y(4660)$, no significant signal of their decay to $\Xi^-\bar \Xi^+$ is found. For these states, upper limits of the products of the branching fraction and the electronic partial width at the 90% confidence level are provided.Comment: 18 pages, 10 pages, 4 table

Amplitude analysis and branching fraction measurement of the decay D+→KS0π+π0π0D^{+} \to K_S^0\pi^+\pi^0\pi^0

Using 2.93 $\rm{fb}^{-1}$ of $e^+e^-$ collision data collected with the BESIII detector at the center-of-mass energy 3.773\,GeV, we perform the first amplitude analysis of the decay $D^+\to K_S^0\pi^+\pi^0\pi^0$ and determine the relative magnitudes and phases of different intermediate processes. The absolute branching fraction of $D^+\to K_S^0\pi^+\pi^0\pi^0$ is measured to be $(2.888\pm0.058_{\rm stat.}\pm0.069_{\rm syst.})\%$. The dominant intermediate processes are $D^+\to K_S^0a_1(1260)^+(\to \rho^+\pi^0)$ and $D^+\to \bar{K}^{*0}\rho^+$, with branching fractions of $(8.66\pm1.04_{\rm stat.}\pm1.39_{\rm syst.})\!\times \!10^{-3}$ and $(9.70\pm0.81_{\rm stat.}\pm0.53_{\rm syst.})\!\times \!10^{-3}$, respectively

A coupled-channel analysis of the X(3872)X(3872) lineshape with BESIII data

We perform a study of the $X(3872)$ lineshape using the data samples of $e^+e^-\to\gamma X(3872)$, $X(3872)\to D^0\bar{D}^0 \pi^0$ and $\pi^+\pi^- J/\psi$ collected with the BESIII detector. The effects of the coupled-channels and the off-shell $D^{*0}$ are included in the parameterization of the lineshape. The lineshape mass parameter is obtained to be $M_{X}=(3871.63\pm 0.13^{+0.06}_{-0.05})$ MeV. Two poles are found on the first and second Riemann sheets corresponding to the $D^{*0}\bar{D}^0$ branch cut. The pole location on the first sheet is much closer to the $D^{*0}\bar{D}^0$ threshold than the other, and is determined to be $7.04\pm0.15^{+0.07}_{-0.08}$ MeV above the $D^0\bar{D}^0\pi^0$ threshold with an imaginary part $-0.19\pm0.08^{+0.14}_{-0.19}$ MeV

Measurement of branching fractions of Λc+\Lambda_{c}^{+} decays to Σ+K+K−\Sigma^{+} K^{+} K^{-}, Σ+ϕ\Sigma^{+}\phi and Σ+K+π−(π0)\Sigma^{+} K^{+} \pi^{-}(\pi^{0})

Based on 4.5 fb$^{-1}$ data taken at seven center-of-mass energies ranging from 4.600 to 4.699 GeV with the BESIII detector at the BEPCII collider, we measure the branching fractions of $\Lambda_{c}^{+}\rightarrow\Sigma^{+}+hadrons$ relative to $\Lambda_{c}^{+}\rightarrow \Sigma^+ \pi^+ \pi^-$. Combining with the world average branching fraction of $\Lambda_{c}^{+}\rightarrow \Sigma^+ \pi^+ \pi^-$, their branching fractions are measured to be $(0.377\pm0.042\pm0.018\pm0.021)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+} K^{+} K^{-}$, $(0.200\pm0.023\pm0.010\pm0.011)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+} K^{+} \pi^{-}$, $(0.414\pm0.080\pm0.029\pm0.023)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+}\phi$ and $(0.197\pm0.036\pm0.008\pm0.011)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+}K^{+} K^{-}$(non-$\phi$). In all the above results, the first uncertainties are statistical, the second are systematic and the third are from external input of the branching fraction of $\Lambda_{c}^{+}\rightarrow \Sigma^+ \pi^+ \pi^-$. Since no signal for $\Lambda_{c}^{+}\rightarrow\Sigma^{+} K^{+} \pi^{-}\pi^{0}$ is observed, the upper limit of its branching fraction is determined to be 0.11\% at the 90$\%$ confidence level

Observation of the Singly Cabibbo-Suppressed Decay Λc+→Σ−K+π+\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}

The singly Cabibbo-suppressed decay $\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}$ is observed for the first time with a statistical significance of $6.4\sigma$ by using 4.5 fb$^{-1}$ of $e^+e^-$ collision data collected at center-of-mass energies between 4.600 and 4.699 GeV with the BESIII detector at BEPCII. The absolute branching fraction of $\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}$ is measured to be $(3.8\pm1.3_{\rm stat}\pm0.2_{\rm syst})\times 10^{-4}$ in a model-independent approach. This is the first observation of a Cabibbo-suppressed $\Lambda_{c}^{+}$ decay involving $\Sigma^-$ in the final state. The ratio of branching fractions between $\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}$ and the Cabibbo-favored decay $\Lambda_{c}^{+}\to \Sigma^- \pi^+\pi^+$ is calculated to be $(0.4 \pm 0.1)s_{c}^{2}$, where $s_{c} \equiv \sin\theta_c = 0.2248$ with $\theta_c$ the Cabibbo mixing angle. This ratio significantly deviates from $1.0s_{c}^{2}$ and provides important information for the understanding of nonfactorization contributions in $\Lambda_{c}^{+}$ decays.Comment: 8 pages, 2 figure