Investigative biological therapies for primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by dryness of the eyes and mouth. The histological feature is mononuclear cell infiltration in exocrine glands, primarily salivary and lachrymal glands. As the disease progresses, some other tissues and organs may be involved and extraglandular manifestations ensue. The major current treatments are palliative and empirical, and in most cases the outcomes are not satisfactory. Emerging data indicate a critical role of lymphocytes in its development and progression. While pioneering work targeting B cells has demonstrated some encouraging results, more trials are warranted to validate the safety and efficacy. In addition, modulation of T cell function with abatacept ameliorates the severity of pSS. Furthermore, clinical trials to inhibit important cytokines involved in its formation have been carried out. In this article, we summarize and compare current biological therapies in order to find new and effective treatments for pSS.

Erythropoietin enhances meniscal regeneration and prevents osteoarthritis formation in mice.

Osteoarthritis (OA) is a leading cause of pain and disability, and knee is the most commonly afflicted joint. Meniscal tear due to injury or degeneration is an established factor for OA pathogenesis. Previous studies have demonstrated that meniscectomy does not reduce the OA incidence. We hypothesized that enhancing meniscal regeneration may prevent OA formation and progression. We first investigated the developmental pattern of mouse meniscus. Knee joint samples were collected at embryonic stages as well as after birth for histological and immunohistochemical studies. The results showed that meniscal cells underwent active proliferation and apoptosis at embryonic day 19.5 and Day 1 after birth. Collagen I (Col-1) is a major type of matrix protein in matured meniscus. Meniscal cells isolated from 3-month-old mice were used to examine the effect of selected factors on the molecules related to cell proliferation, angiogenesis, inflammation, extracellular matrix proteins and matrix degradation enzymes. Overall assessment indicated that EPO had optimal effect on meniscal regeneration. An organ culture system of mouse meniscus was established to test the effect of EPO on in vitro cultured menisci. EPO upregulated the expression of Col-1, Col-2 and VEGF-A, and downregulated the expression of MMP-13. Finally, we established a mouse model of meniscus injury induced OA (MIO), and mice were subjected to PBS or EPO treatments. The results demonstrated that EPO enhanced meniscal repair and prevented OA formation. EPO may become an effective Disease Modifying Osteoarthritis Drug and may be used for early treatment for meniscal injury to prevent OA progression.

Rigid Organization of Fluorescence-Active Ligands by Artificial Macrocyclic Receptor to Achieve the Thioflavin T-Amyloid Fibril Level Association.

The push-pull molecules with an intramolecular charge transfer from donor to acceptor sides upon excitation exhibit a wide variety of biological and electronic activities, as exemplified by the in vivo fluorescence imaging probes for amyloid fibrils in the diagnosis and treatment of amyloid diseases. Interestingly, the structurally much simpler bis(4,8-disulfonato-1,5-naphtho)-32-crown-8 (DNC), in keen contrast to the conventional macrocyclic receptors, was found to dramatically enhance the fluorescence of twisted intramolecular charge-transfer molecules possessing various benzothiazolium and stilbazolium fluorophores upon complexation. Spectroscopic and microcalorimetric titrations jointly demonstrated the complex structures and the interactions that promote the extremely strong complexation, revealing that the binding affinity in these artificial host-guest pairs could reach up to a nearly 10(7) M(-1) order of magnitude in water, and the sandwich-type complexation is driven by electrostatic, hydrophobic, π-stacking, and hydrogen-bonding interactions. Quantum chemical calculations on free molecules and their DNC-bound species in both the ground and excited states elucidated that the encapsulation by DNC could greatly deter the central single and double chemical bonds from free intramolecular rotation in the singlet excited state, thus leading to the unique and unprecedented fluorescence enhancement upon sandwich-type complexation. This complexation-induced structural reorganization mechanism may also apply to the binding of other small-molecule ligands by functional receptors and contribute to the molecular-level understanding of the receptor-ligand interactions in many biology-related systems.

Nickel-Catalyzed Hydroacylation of Styrenes with Simple Aldehydes: Reaction Development and Mechanistic Insights.

The first nickel-catalyzed intermolecular hydroacylation reaction of alkenes with simple aldehydes has been developed. This reaction offers a new approach to the selective preparation of branched ketones in high yields (up to 99%) and branched selectivities (up to 99:1). Experimental data provide evidence for reversible formation of acyl-nickel-alkyl intermediate, and DFT calculations show that the aldehyde C-H bond transfer to a coordinated alkene without oxidative addition is involved. The origin of the reactivity and regioselectivity of this reaction was also investigated computationally, which are consistent with experimental observations.

[IR spectral-analysis-based range estimation for an object with small temperature difference from background].

It is a typical passive ranging technology that estimation of distance of an object is based on transmission characteristic of infrared radiation, it is also a hotspot in electro-optic countermeasures. Because of avoiding transmitting energy in the detection, this ranging technology will significantly enhance the penetration capability and infrared conceal capability of the missiles or unmanned aerial vehicles. With the current situation in existing passive ranging system, for overcoming the shortage in ranging an oncoming target object with small temperature difference from background, an improved distance estimation scheme was proposed. This article begins with introducing the concept of signal transfer function, makes clear the working curve of current algorithm, and points out that the estimated distance is not unique due to inherent nonlinearity of the working curve. A new distance calculation algorithm was obtained through nonlinear correction technique. It is a ranging formula by using sensing information at 3-5 and 8-12 microm combined with background temperature and field meteorological conditions. The authors' study has shown that the ranging error could be mainly kept around the level of 10% under the condition of the target and background apparent temperature difference equal to +/- 5 K, and the error in estimating background temperature is no more than +/- 15 K.

catena-Poly[[[diaqua-copper(II)]-bis-[µ-1,5-bis-(1H-imidazol-1-yl)pentane-κ(2) N (3):N (3')]] naphthalene-1,5-disulfonate].

In the title complex, {[Cu(C11H16N4)2(H2O)2](C10H6O6S2)} n , the Cu(II) atom, lying on an inversion center, is six-coordinated by two water mol-ecules and four N atoms from four 1,5-bis-(1H-imidazol-1-yl)pentane (biim-5) ligands in a distorted octa-hedral geometry. Adjacent Cu(II) atoms are linked by two biim-5 ligands, forming a chain along [111]. Two atoms of the pentane group are disordered over two sets of sites, with an occupancy ratio of 0.554 (18):0.446 (18). Inter-molecular O-H⋯O hydrogen bonds link the chains and the centrosymmetric naphthalene-1,5-disulfonate anions into a layer structure parallel to (0-11).