Acupuncture for hot flashes in hormone receptor-positive breast cancer: A pooled analysis of individual patient data from parallel randomized trials.

BACKGROUND: Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. METHODS: Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)-Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT-Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. RESULTS: In total, 158 women with stage 0-III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p = .0003), the hot flash score (-5.3 ± 0.9 vs. -1.4 ± 0.9; p < .003), and the FACT-Breast total score (8.0 ± 1.6 vs. -0.01 ± 1.6; p = .0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p = .005). CONCLUSIONS: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea.

Establishing an Integrative Oncology Service: Essential Aspects of Program Development.

PURPOSE OF REVIEW: Over the last 2 decades, integrative oncology (IO) has seen exponential growth within cancer care. It aims to combine evidence-based complementary therapies with conventional treatments to improve the well-being and quality of life for individuals dealing with cancer. The proliferation of integrative medicine programs in major cancer centers globally reflects varying approaches shaped by cultural, demographic, and resource-based factors. RECENT FINDINGS: Drawing upon the expertise of leaders in IO from the Society for Integrative Oncology (SIO) Clinical Practice Committee, this manuscript serves as a practical guide for establishing an IO practice. Collating insights from diverse professionals, including oncologists, integrative oncologists, supportive care physicians, researchers, and clinicians, the paper aims to provide a comprehensive roadmap for initiating and advancing IO services. The primary objective is to bridge the gap between conventional cancer care and complementary therapies, fostering a patient-centric approach to address the multifaceted challenges encountered by individuals with cancer. This paper delineates several key sections elucidating different aspects of IO practice. It delves into the core components necessary for an IO service's foundation, outlines the initial medical consultation process, and presents crucial tools essential for successful consultations. By consolidating insights and expertise, this manuscript seeks to facilitate the integration of IO into mainstream cancer care, ultimately enhancing patient outcomes and experiences.

Virtual acupressure for symptom management in cancer populations during COVID-19: a retrospective analysis.

OBJECTIVE: Following the outbreak of COVID-19, access to in-person oncology acupuncture service was temporarily disrupted at Dana-Farber Cancer Institute, a National Cancer Institute (NCI)-designated cancer center. During this period, a virtual acupuncturist-guided session of patient self-acupressure was implemented to provide continuity of supportive care for cancer patients. We provide preliminary findings on the feasibility and potential impact of remotely delivered acupressure on patient-reported symptom burden in cancer populations. METHODS: This is a retrospective chart review of cancer patients who received virtual acupressure service at a single academic cancer center from May 11 to December 31, 2020. Each telehealth session consisted of a one-on-one appointment between the patient and acupuncturist. A semi-standardized set of acupoints were used, including Yintang, ST36, GB20, PC6, and HT7 as well as Relaxation Point on the ear. At the start of each session, Edmonton Symptom Assessment System (ESAS) was used to collect patient-reported symptom burden. For patients with at least one follow-up within 14 days of the baseline visit, paired t-test was used to analyze changes in ESAS scores from baseline to first follow-up. RESULTS: A total of 102 virtual acupressure sessions were administered to 32 patients. Most patients were females (90.6%) and white (84.4%), and the mean age was 55.7 (range = 26-82; SD = 15.7). The most common cancer diagnosis was breast (53.1%), followed by pancreatic (12.5%) and lung (9.4%). Baseline ESAS Total, Physical, and Emotional scores were 21.5 (SD = 11.1), 12.4 (SD = 7.5), and 5.2 (SD = 3.8), respectively. Of 32 patients, 13 (41%) had a second acupressure session within 14 days. For these 13 patients, there was a statistically significant reduction in Total symptom burden (-4.9 ± 7.6; p = 0.04) and in Physical (-3.5 ± 5.4; p = 0.04) and Emotional (-1.2 ± 1.8; p = 0.03) subscales from baseline to follow-up. CONCLUSION: Virtual acupressure was associated with significant reduction in symptom burden among cancer patients from their baseline to follow-up visits. Larger scale randomized clinical studies are needed to confirm these findings and better understand the impact of virtual acupressure on symptom burden in cancer populations.

Role of carnitine in adaptation of Chromohalobacter salexigens DSM 3043 and its mutants to osmotic and temperature stress in defined medium.

L-Carnitine is widespread in nature, but little information is available on its metabolism and physiological functions in moderate halophiles. In this study, we found that Chromohalobacter salexigens DSM 3043 could utilize carnitine not only as a nutrient, but also as an osmolyte. When grown at 37 °C under salt-stress conditions, the strain utilized carnitine as an osmoprotectant by enzymatically converting it into GB. When grown at low and high temperature, both carnitine and its metabolic intermediate GB were simultaneously accumulated intracellularly, serving as cryoprotectants and thermoprotectants. The genes (csal_3172, csal_3173, and csal_3174) which were predicted to participate in L-carnitine degradation to GB were deleted to construct the corresponding mutants. The effects of salinity and temperature on the growth rates and cytoplasmic solute pools of the C. salexigens wild-type and mutant strains were investigated. 13C-NMR analysis revealed that GB was still detected in the Δcsal_3172Δcsal_3173Δcsal_3174 mutant grown in a defined medium with added DL-carnitine, but not with L-carnitine, indicating that an unidentified D-carnitine degradation pathway exists in C. salexigens. Taken together, the data presented in this study expand our knowledge on carnitine metabolism and its physiological functions in C. salexigens exposed to single or multiple environmental abiotic stress.

Photoredox-Catalyzed Cascade of o-Hydroxyarylenaminones to Access 3-Aminated Chromones.

Reported herein is a photoredox-catalyzed amination of o-hydroxyarylenaminones with tert-butyl ((perfluoropyridin-4-yl)oxy)carbamate, a versatile amidyl-radical precursor developed in our laboratory. This work establishes a new cascade pathway for the assembly of a range of 3-aminochromones under mild conditions. Downstream transformations of the obtained 3-aminochromones to construct diverse amino pyrimidines greatly broaden the applications of this photocatalyzed protocol.

Targeted Luminescent Probes for Precise Upconversion/NIR II Luminescence Diagnosis of Lung Adenocarcinoma.

In this research, the antibody of the searched hub genes has been proposed to combine with a rare-earth composite for an upconversion luminescence (UCL) and downconversion (DCL) NIR-II imaging strategy for the diagnosis of lung adenocarcinoma (LUAD). Weighted gene co-expression network analysis is used to search the most relevant hub genes, and the required top genes that contribute to tumorigenesis (negative: CLEC3B, MFAP4, PECAM1, and FHL1; positive: CCNB2, CDCA5, HMMR, and TOP2A) are identified and validated by survival analysis and transcriptional and translational results. Meanwhile, fluorescence imaging probes (NaYF4:Yb,Er,Eu@NaYF4:Nd, denoted as NYF:Eu NPs) with multimodal optical imaging properties of downconversion and upconversion luminescence in the visible region and luminescence in the near infrared II region are designed with various uniform sizes and enhanced penetration and sensitivity. Finally, when the NYF:Eu NP probe is combined with antibodies of these chosen positive hub genes (such as, TOP2A and CCNB2), the in vitro and in vivo animal experiments (flow cytometry, cell counting kit-8 assay using A549 cells, and in vivo immunohistochemistry IHC microscopy images of LUAD from patient cases) indicate that the designed nanoprobes can be excellently used as a targeted optical probe for future accurate diagnosis and surgery navigation of LUAD in contrast with other cancer cells and normal cells. This strategy of antibodies combined with optical probes provides a dual-modal luminescence imaging method for precise medicine.

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Survivors: A Randomized Controlled Pilot Trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating long-term side effects in breast cancer survivors. We conducted a randomized controlled pilot trial to assess the feasibility, safety, and effects of an acupuncture intervention on CIPN in this population. PATIENTS AND METHODS: Women with stage I-III breast cancer with grade 1 or higher CIPN after taxane-containing adjuvant chemotherapy were randomized 1:1 to an immediate acupuncture (IA) arm or to a waitlist control group (CG). Participants in the IA arm received 18 sessions of acupuncture over 8 weeks, then received no additional acupuncture. Patients in the CG arm received usual care over 8 weeks, followed by nine sessions of acupuncture over 8 weeks. Measures including Patient Neurotoxicity Questionnaire (PNQ), Functional Assessment of Cancer Therapy-Neurotoxicity subscale (FACT-NTX), and Brief Pain Inventory-short form (BPI-SF) were collected at baseline and at 4, 8, and 16 weeks after enrollment. RESULTS: Forty women (median age, 54) were enrolled (20 to IA and 20 to CG), with median time between completion of chemotherapy and enrollment of 14 months (range 1-92). At 8 weeks, participants in the IA arm experienced significant improvements in PNQ sensory score (-1.0 ± 0.9 vs. -0.3 ± 0.6; p = .01), FACT-NTX summary score (8.7 ± 8.9 vs. 1.2 ± 5.4; p = .002), and BPI-SF pain severity score (-1.1 ± 1.7 vs. 0.3 ± 1.5; p = .03), compared with those in the CG arm. No serious side effects were observed. CONCLUSION: Women with CIPN after adjuvant taxane therapy for breast cancer experienced significant improvements in neuropathic symptoms from an 8-week acupuncture treatment regimen. Additional larger studies are needed to confirm these findings. IMPLICATIONS FOR PRACTICE: Chemotherapy-induced peripheral neuropathy (CIPN) is a toxicity that often persists for months to years after the completion of adjuvant chemotherapy for early breast cancer. In a randomized pilot trial of 40 breast cancer survivors with CIPN, an 8-week acupuncture intervention (vs. usual care) led to a statistically and clinically significant improvement in subjective sensory symptoms including neuropathic pain and paresthesia. Given the lack of effective therapies and established safety profile of acupuncture, clinicians may consider acupuncture as a treatment option for mild to moderate CIPN in practice.

Role of N,N-Dimethylglycine and Its Catabolism to Sarcosine in Chromohalobacter salexigens DSM 3043.

Chromohalobacter salexigens DSM 3043 can grow on N,N-dimethylglycine (DMG) as the sole C, N, and energy source and utilize sarcosine as the sole N source under aerobic conditions. However, little is known about the genes and enzymes involved in the conversion of DMG to sarcosine in this strain. In the present study, gene disruption and complementation assays indicated that the csal_0990, csal_0991, csal_0992, and csal_0993 genes are responsible for DMG degradation to sarcosine. The csal_0990 gene heterologously expressed in Escherichia coli was proven to encode an unusual DMG dehydrogenase (DMGDH). The enzyme, existing as a monomer of 79 kDa with a noncovalently bound flavin adenine dinucleotide, utilized both DMG and sarcosine as substrates and exhibited dual coenzyme specificity, preferring NAD+ to NADP+ The optimum pH and temperature of enzyme activity were determined to be 7.0 and 60°C, respectively. Kinetic parameters of the enzyme toward its substrates were determined accordingly. Under high-salinity conditions, the presence of DMG inhibited growth of the wild type and induced the production and accumulation of trehalose and glucosylglycerate intracellularly. Moreover, exogenous addition of DMG significantly improved the growth rates of the four DMG- mutants (Δcsal_0990, Δcsal_0991, Δcsal_0992, and Δcsal_0993) incubated at 37°C in S-M63 synthetic medium with sarcosine as the sole N source. 13C nuclear magnetic resonance (13C-NMR) experiments revealed that not only ectoine, glutamate, and N-acetyl-2,4-diaminobutyrate but also glycine betaine (GB), DMG, sarcosine, trehalose, and glucosylglycerate are accumulated intracellularly in the four mutants.IMPORTANCE Although N,N-dimethylglycine (DMG) dehydrogenase (DMGDH) activity was detected in cell extracts of microorganisms, the genes encoding microbial DMGDHs have not been determined until now. In addition, to our knowledge, the physiological role of DMG in moderate halophiles has never been investigated. In this study, we identified the genes involved in DMG degradation to sarcosine, characterized an unusual DMGDH, and investigated the role of DMG in Chromohalobacter salexigens DSM 3043 and its mutants. Our results suggested that the conversion of DMG to sarcosine is accompanied by intramolecular delivery of electrons in DMGDH and intermolecular electron transfer between DMGDH and other electron acceptors. Moreover, an unidentified methyltransferase catalyzing the production of glycine betaine (GB) from DMG but sharing no homology with the reported sarcosine DMG methyltransferases was predicted to be present in the cells. The results of this study expand our understanding of the physiological role of DMG and its catabolism to sarcosine in C. salexigens.

Cloning and heterologous expression of a novel halo/alkali-stable multi-domain xylanase (XylM18) from a marine bacterium Marinimicrobium sp. strain LS-A18.

Halophilic bacteria are good bioresources for halotolerant alkaline enzymes. A multi-domain high-molecular-weight endo-ß-1,4-xylanase gene, xylM18, was cloned from a halophilic marine bacterium Marinimicrobium sp. LS-A18. XylM18 is different from any of the functionally reported xylanases. It has a glycosyl hydrolase (GH) 43 domain, a GH10 domain, and two serine-rich linkers, representing a novel family. The gene, encoding 1022 residues, was cloned and heterologously expressed in Escherichia coli BL21(DE3) cells. Purified XylM18 was proved to be a xylanase. It showed diminished activity without salt and showed activity with a broad NaCl range from 0.2 to 25% (w/v). NaCl can increase the optimal temperature from 30 °C (0% NaCl) to 50 °C (10% NaCl). The purified XylM18 was active between pH 6.0 and 10.0 and was optimally active at pH 7.0. The xylanase activities were basically unchanged at a NaCl concentration range from 10 to 20% or pH from 7 to 10 after 24 h incubation. The apparent Km and Vmax values of XylM18 for xylan were 2.76 mg/mL and 60.0 U/mg, respectively. The GH10 domain of this enzyme, XylM18-GH10, was expressed and characterized. XylM18-GH10 also showed xylanase activity and maintained halo-stable property. The apparent Km and Vmax values of XylM18-GH10 for xylan were 1.60 mg/mL and 130.1 U/mg, respectively. Other domains of XylM18 showed no xylanase activity. In summary, XylM18 is a halo-tolerant and alkali-stable endoxylanase which is a suitable candidate for xylan biodegradation in high-salt and alkali conditions. To our knowledge, this is the first report of a multidomain high-molecular-weight xylanase.

Glycine Betaine Monooxygenase, an Unusual Rieske-Type Oxygenase System, Catalyzes the Oxidative N-Demethylation of Glycine Betaine in Chromohalobacter salexigens DSM 3043.

Although some bacteria, including Chromohalobacter salexigens DSM 3043, can use glycine betaine (GB) as a sole source of carbon and energy, little information is available about the genes and their encoded proteins involved in the initial step of the GB degradation pathway. In the present study, the results of conserved domain analysis, construction of in-frame deletion mutants, and an in vivo functional complementation assay suggested that the open reading frames Csal_1004 and Csal_1005, designated bmoA and bmoB, respectively, may act as the terminal oxygenase and the ferredoxin reductase genes in a novel Rieske-type oxygenase system to convert GB to dimethylglycine in C. salexigens DSM 3043. To further verify their function, BmoA and BmoB were heterologously overexpressed in Escherichia coli, and 13C nuclear magnetic resonance analysis revealed that dimethylglycine was accumulated in E. coli BL21(DE3) expressing BmoAB or BmoA. In addition, His-tagged BmoA and BmoB were individually purified to electrophoretic homogeneity and estimated to be a homotrimer and a monomer, respectively. In vitro biochemical analysis indicated that BmoB is an NADH-dependent flavin reductase with one noncovalently bound flavin adenine dinucleotide (FAD) as its prosthetic group. In the presence of BmoB, NADH, and flavin, BmoA could aerobically degrade GB to dimethylglycine with the concomitant production of formaldehyde. BmoA exhibited strict substrate specificity for GB, and its demethylation activity was stimulated by Fe2+ Phylogenetic analysis showed that BmoA belongs to group V of the Rieske nonheme iron oxygenase (RO) family, and all the members in this group were able to use quaternary ammonium compounds as substrates.IMPORTANCE GB is widely distributed in nature. In addition to being accumulated intracellularly as a compatible solute to deal with osmotic stress, it can be utilized by many bacteria as a source of carbon and energy. However, very limited knowledge is presently available about the molecular and biochemical mechanisms for the initial step of the aerobic GB degradation pathway in bacteria. Here, we report the molecular and biochemical characterization of a novel two-component Rieske-type monooxygenase system, GB monooxygenase (BMO), which is responsible for oxidative demethylation of GB to dimethylglycine in C. salexigens DSM 3043. The results gained in this study extend our knowledge on the catalytic reaction of microbial GB degradation to dimethylglycine.

A novel gene, encoding 3-aminobenzoate 6-monooxygenase, involved in 3-aminobenzoate degradation in Comamonas sp. strain QT12.

The biodegradation pathway of 3-aminobenzoate has been documented, but little is known about the sequence and biochemical properties of the proteins involved. In the present study, a 10,083-bp DNA fragment involved in 3-aminobenzoate degradation was identified in 3-aminobenzoate-degrading Comamonas sp. strain QT12. The mabA gene, whose encoded protein shares 39% amino acid sequence identity with 3-hydroxybenzoate 6-hydroxylase of Polaromonas naphthalenivorans CJ2, was identified on this DNA fragment, and the mabA-disrupted mutant was unable to grow on and convert 3-aminobenzoate. MabA was heterologously expressed in Escherichia coli and purified to homogeneity as an approximately ~ 48-kDa His-tagged protein. It was characterized as 3-aminobenzoate 6-hydroxylase capable of catalyzing the conversion of 3-aminobenzoate to 5-aminosalicylate, incorporating one oxygen atom from dioxygen into the product. It contains a non-covalent but tightly bound FAD as the prosthetic group and NADH as an external electron donor. 5-Aminosalicylate was produced with equimolar consumption of NADH. The apparent Km and kcat values of the purified enzyme for 3-aminobenzoate were 158.51 ± 4.74 µM and 6.49 ± 0.17 s-1, respectively, and those for NADH were 189.85 ± 55.70 µM and 7.41 ± 1.39 s-1, respectively. The results suggest that mabA is essential for 3-aminobenzoate degradation in strain QT12, and that 3-aminobenzoate is the primary and physiological substrate of MabA.

Reclassification of Bacillus saliphilus as Alkalicoccus saliphilus gen. nov., comb. nov., and description of Alkalicoccus halolimnae sp. nov., a moderately halophilic bacterium isolated from a salt lake.

A Gram-stain-positive, cocci-shaped, non-spore-forming and moderately halophilic bacterium, designed BZ-SZ-XJ29T, was isolated from a salt lake of China. On the basis of 16S rRNA gene sequence similarity, the closest phylogenetic relatives were Bacillus saliphilus 6AGT (97.3 % 16S rRNA gene sequence similarity) and five other species of the genus Bacillus(95.4-96.3 %). However, strain BZ-SZ-XJ29T shared only 89.5 % 16S rRNA gene sequence similarity with Bacillus subtilis subsp. subtilis DSM 10T, indicating that this isolate might not be a member of the genus Bacillus. The genomic DNA G+C content was 40.0 mol% (Tm). The DNA-DNA relatedness value with B. saliphilus 6AGT was 45±2 %. Strain BZ-SZ-XJ29T formed yellow pigment and grew in the presence of 0.74-4.15 M Na+ [optimum 1.42-2.10 M Na+], at pH 6.0-10.5 (optimum pH 7.5), and at 5-41 °C (optimum 33 °C). The predominant (>10 %) fatty acids were anteiso-C15 : 0 and anteiso-C15 : 0. The dominant polar lipids consisted of diphosphatidylglycerol and the respiratory quinone was menaquinone-7 (MK-7). The peptidoglycan type of the cell wall was A1γ, based on meso-diaminopimelic acid as the diagnostic diamino acid. On the basis of the combined phylogenetic data, phenotypic features and chemotaxonomic properties, it is proposed that B. saliphilus and strain BZ-SZ-XJ29T should be assigned to a single novel genus as two separate species. Bacillus. saliphilus is reclassified in a new genus, Alkalicoccus gen. nov., as Alkalicoccus saliphilus comb. nov., and is the type species of the new genus; the type strain of the type species is 6AGT (=DSM 15402T=ATCC BAA-957T). Strain BZ-SZ-XJ29T (=DSM 29191T=JCM 30193T=CGMCC 1.12936T) is placed in the genus Alkalicoccus as a novel species, Alkalicoccus halolimnae sp. nov.

Establishment of a markerless gene deletion system in Chromohalobacter salexigens DSM 3043.

Chromohalobacter salexigens DSM 3043 can grow over a wide range of salinity, which makes it as an excellent model organism for understanding the mechanism of prokaryotic osmoregulation. Functional analysis of C. salexigens genes is an essential way to reveal their roles in cellular osmoregulation. However, the lack of an effective markerless gene deletion system has prevented construction of multiple gene deletion mutants for the members in the genus. Here, we report the development of a markerless gene deletion system in C. salexigens using allelic exchange method. In this system, the in vitro mutant allele of target gene was inserted into a pK18mobsacB-based integrative vector pMDC21, which contained a chloramphenicol resistance cassette as the positive selection marker and a sacB gene from Bacillus subtilis as the counterselectable marker. To validate this system, two single-gene deletion mutants and a double-gene deletion mutant were constructed. In addition, our results showed that growth of the merodiploids and sucrose screening at 25 °C were more effective to decrease the occurrence of spontaneous sucrose resistance colonies than at higher temperature (30 or 37 °C), and growth of the merodiploids in mineral salt medium instead of the complex medium was critical to increase the recovery rate of deletion mutants.

Acupuncture for Chemoradiation Therapy-Related Dysphagia in Head and Neck Cancer: A Pilot Randomized Sham-Controlled Trial.

INTRODUCTION: Dysphagia is common in head and neck cancer patients after concurrent chemoradiation therapy (CRT). This study evaluated the feasibility of conducting a randomized sham-controlled trial and collected preliminary data on safety and efficacy of acupuncture. PATIENTS AND METHODS: Head and neck cancer (HNC) patients with stage III-IV squamous cell carcinoma were randomized to 12 sessions of either active acupuncture (AA) or sham acupuncture (SA) during and following CRT. Patients were blinded to treatment assignment. Swallowing-related quality of life (QOL) was assessed using the MD Anderson Dysphagia Inventory (MDADI) total and subscale scores. RESULTS: Multiple aspects of trial feasibility were confirmed. Forty-two of 196 patients screened (21%) were enrolled and randomized to receive AA (n = 21) or SA (n = 21); 79% completed at least 10 of 12 planned acupuncture sessions; 81% completed the study follow-ups. The majority of patients reported uncertainty regarding their treatment assignment, with no difference between the AA and SA groups. Audits confirmed both AA and SA treatments were delivered with high fidelity. No serious acupuncture-related side effects were observed. MDADI total scores significantly improved from baseline to 12 months post-CRT in both groups (AA: +7.9; SA +13.9; p = .044, p < .001). Similar patterns were observed for the MDADI global subscale (AA: +25.0; SA +22.7; p = .001, p = .002). Intent-to-treat analyses suggested no difference between the treatment groups (p = .17, p = .76 for MDADI total and global scores, respectively). CONCLUSION: A sham-controlled randomized trial evaluating acupuncture in dysphagia-related QOL in HNC found the procedure to be feasible and safe. Further investigation is required to evaluate efficacy. IMPLICATIONS FOR PRACTICE: Dysphagia or swallowing difficulty is an important and common condition after concurrent chemoradiation therapy in head and neck cancer patients. In addition to current available supportive care, acupuncture may offer potential for treating dysphagia. This study demonstrated that both active acupuncture and sham acupuncture are safe and were associated with improved dysphagia-related quality of life from baseline to 12 months after concurrent chemoradiation therapy. This study was not designed to inform underlying specific versus nonspecific effects. Future larger-scale pragmatic clinical trials evaluating the effectiveness of acupuncture versus standard of care are warranted, and further mechanistic research is needed to understand how active versus purportedly sham acupuncture procedures affect dysphagia-related symptoms.

Salinomycin radiosensitizes human nasopharyngeal carcinoma cell line CNE-2 to radiation.

Nasopharyngeal carcinoma (NPC) is primarily treated by chemoradiation. However, how to promote radiation sensitivity in NPC remains a challenge. Salinomycin is potentially useful for the treatment of cancer. This study aimed to explore the radiosensitivity of salinomycin on human nasopharyngeal carcinoma cell line CNE-2. CNE-2 were treated with salinomycin or irradiation, alone or in combination. The cytotoxicity effects of salinomycin were measured using CCK-8 assay. Clonogenic survival assay was used to evaluate the effects of salinomycin on the radiosensitivity of CNE-2. The changes of cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of Caspase3/Bax/Bal-2 was detected by Western blotting. DNA damage was detected via γ-H2AX foci counting. The results showed that salinomycin induced apoptosis and G2/M arrest, increased Bax and cleaved Caspase3, decreased Bcl-2 expression, and increased the formation of γ-H2AX nuclear foci. These data suggest that salinomycin may be a radiosensitizer for NPC radiotherapy.

Halomonas urumqiensis sp. nov., a moderately halophilic bacterium isolated from a saline-alkaline lake.

A moderately halophilic, aerobic bacterium, strain BZ-SZ-XJ27T, belonging to the genus Halomonas, was isolated from a saline-alkaline lake in the Xinjiang Uyghur Autonomous Region of China. Phylogenetic analysis based on 16S rRNA gene sequences and a multilocus sequence analysis using the 16S rRNA, gyrB and rpoD genes demonstrated that strain BZ-SZ-XJ27T represents a member of the genus Halomonas. On the basis of 16S rRNA gene sequence similarity, the closest relatives were Halomonas campaniensis 5AGT, H. fontilapidosi 5CRT, H. korlensis XK1T and H. sinaiensis ALO SharmT, with similarities of 96.2-97.2 %. DNA-DNA hybridization with H. korlensis CGMCC 1.6981T (the nearest phylogenetic neighbour) and H. campaniensis DSM 15293T (the highest 16S rRNA gene sequence similarity) showed relatedness values of 53 and 38 %, respectively, demonstrating the separateness of the three taxa. The bacterium stained Gram-negative and the cells were motile and rod-shaped. The strain formed creamy-white colonies and grew under optimal conditions of 1.42 M Na+ (range 0.22-4.32 M Na+), pH 8.0-8.5 (range pH 6.0-10.0) and 39 °C (range 4-43 °C). The dominant fatty acids were summed feature 8 (C18 : 1ω7c/C18 : 1ω6c; 36.6 %), C16 : 0 (25.9 %) and summed feature 3 (C16 : 1ω7c/C16 : 1ω6c; 21.2 %). The dominant polar lipids were two unknown phospholipids, phosphatidylethanolamine and phosphatidylglycerol, and the main respiratory quinones were ubiquinone 9 (Q-9; 89 %) and ubiquinone 8 (Q-8; 10 %). The genomic DNA G+C content was 61.7 ± 0.8 mol% (Tm). On the basis of phenotypic, chemotaxonomic and phylogenetic features, strain BZ-SZ-XJ27T is proposed to represent a novel species, Halomonas urumqiensis sp. nov., within the genus Halomonas of the family Halomonadaceae. The type strain is BZ-SZ-XJ27T ( = JCM 30202T = CGMCC 1.12917T).

Identification of important charged residues for alkali cation exchange or pH regulation of NhaH, a Na(+)/H(+) antiporter of Halobacillus dabanensis.

NhaH is a novel Na(+)/H(+) antiporter identified from the moderate halophile Halobacillus dabanensis. In this study, six conserved charged residues located in the putative transmembrane segments (TMS) including TMSV, TMSVI, TMSVIII and TMSXI of NhaH as well as two His residues in Loop III were replaced by site-directed mutagenesis for the identification of their potential roles in the antiport activity and pH regulation. Substitutions D137A, D166A and R325A caused a complete loss of Na(+)(Li(+))/H(+) antiport activity, revealing that D137, D166 and R325 are indispensable for the antiport activity. Substitution D137E led to a significant increase of the apparent Km values for Na(+) and Li(+) without affecting the changes of pH profile, confirming that D137 plays vital roles in alkali cation binding/translocation. Substitution D166E resulted in not only a significant increase of the apparent Km values for Na(+) and Li(+) but also an alkaline shift of pH profile, suggesting that D166 is involved in alkali cation binding/translocation as well as H(+) binding or pH regulation. Substitutions E161N, D224A and D224E caused a significant increase of Km for Na(+) and Li(+), indicating that E161 and D224 partly contribute to alkali cation binding/translocation. Substitution E229K caused an over 50% elevation of the apparent Km for Li(+), without affecting that for Na(+), suggesting that E229 may be mainly responsible for Li(+) binding/translocation. Substitutions H87A and H88A resulted in an acidic shift of pH profile without an effect on Km for Na(+) and Li(+), indicating that H87 and H88 are involved in H(+) binding or pH regulation.

SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer.

Lung cancer is one of the leading causes of cancer-related death in developed countries. Despite decades of intensive efforts to comate this malignant disease, the prognosis of lung cancer remains unfavorable and is especially poor in advanced non-small cell lung cancer (NSCLC). Accumulating evidence indicate that one of the main causes of the poor outcome in NSCLC treatment is the innate resistance of NSCLC patients to anticancer drugs. However, the mechanism underling NSCLC development and drug resistance is not fully understood. Here we show that the mitochondrial class III NAD(+)-dependent deacetylase SIRT5 is overexpressed in human NSCLC and high expression of SIRT5 predicts poor survival. SIRT5 knockdown represses lung cancer cell growth and transformation in vitro and in vivo. Furthermore, we find that SIRT5 knockdown makes lung cancer cells more sensitive to drug (cis-diamminedichloroplatinum [CDDP], 5-fluorouracil [5-FU] or bleomycin) treatment in vitro and in vivo. Mechanically, we identify Nrf2, which is a core transcription factor for lung cancer growth and drug resistance, as a target of SIRT5. SIRT5 mRNA level is positively correlated with the expression of Nrf2 in lung cancer tissues and SIRT5 knockdown reduces the expression of Nrf2 and its downstream drug-resistance genes. Taken together, our findings implicate that SIRT5 as a protein responsible for growth and drug resistance in human NSCLC, and SIRT5 may serve as a potential prognostic factor and drug target for intervention.

High expression of CASK correlates with progression and poor prognosis of colorectal cancer.

Calcium/calmodulin-dependent serine protein kinase (CASK), which localizes at cell-cell adhesion sites and binds to the heparan sulfate proteoglycan syndecan-2, is involved in cell proliferation, cytoskeletal remodeling, and cell migration. To demonstrate the role of CASK in colorectal cancer (CRC) carcinogenesis, we examined the expression of CASK and its binding protein syndecan-2 in human CRC tissues. The expression of CASK was measured in CRC specimens and the controls from adenomas and normal mucosae by immunohistochemical staining and Western blot analysis. Syndecan-2 protein level was tested in CRC samples and the controls by Western blot analysis. The correlations between CASK expression and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analyzed. Compared to the controls, both CASK and syndecan-2 expression were enhanced in CRC tissues. Furthermore, high expression of CASK and syndecan-2 was significantly correlated with advanced tumor stage, lymphatic invasion, lymph node metastasis, vascular invasion, liver metastasis, and unresectable metastatic CRC. Survival analysis showed that patients with low CASK staining had a significantly better survival compared to patients with high CASK staining. In multivariate analysis, CASK overexpression, advanced tumor stage, lymph node metastasis, vasvular invasion, and liver metastasis were independent prognostic factors of poor DFS and OS. Our present study indicates that CASK overexpression is associated with an unfavorable prognosis. CASK is an independent prognostic factor for CRC, which suggests that it is a novel and crucial predictor for CRC metastasis.